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.

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.

Reactivity of serum IgG anti-GM1 ganglioside antibodies with the lipopolysaccharide fractions of Campylobacter jejuni isolates from patients with Guillain-Barre syndrome (GBS).

Campylobacter jejuni (Cj) enteritis is the most frequently recognised infection preceding Guillain-Barre syndrome (GBS) and this combination is commonly associated with anti-GM1 ganglioside (anti-GM1) antibodies. We have examined the hypothesis that the anti-GM1 antibodies represent an immune response against the Cj lipopolysaccharide (LPS). We prepared the LPS fraction from 8 isolates of Cj, 3 from GBS patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 3 from patients with Miller Fisher syndrome (MFS) and 2 from enteritis patients without neurological disease. We looked for IgG antibodies against LPS and GM1 in the serum of 10 GBS and 10 MFS patients, including the patients from whom the Cj had been isolated, and 11 normal control subjects. The highest levels of IgG binding to LPS fractions were found in the GBS patient sera and were with one of the LPS fractions extracted from the C. jejuni isolated from a GBS patient, one from a MFS patient and two Cj isolates from enteritis patients without neurological disease. The level of IgG binding to these LPS fractions was related to the level of IgG anti-GM1 antibody in the serum. Affinity-purified anti-GM1 antibodies showed the same pattern of differential binding to the LPS fractions as the serum from which they were derived. Cholera toxin bound to the same LPS fractions as GBS patients' IgG, the binding of which was blocked by the toxin indicating specific antibody reactivity with a GM1 hapten. The presence of serum anti-GM1 antibodies did not coincide with the presence of the GM1 hapten on the LPS of the infecting strain of Campylobacter indicating that anti-GM1 antibodies do not necessarily arise as part of a simple immune response against the LPS. The IgG antibodies binding to LPS were predominantly of the IgG2 isotype but patients with anti-GM1 IgG had mainly antibodies of IgG1 subclass against both LPS and GM1, implying their production by a T-cell dependent mechanism.

HLA-class II alleles in Guillain-Barré syndrome and Miller Fisher syndrome and their association with preceding Campylobacter jejuni infection.

HLA typing for class II alleles was performed on 97 patients with Guillain-Barré syndrome or Miller Fisher syndrome and compared with 100 controls. There was a significant association between HLA-DQB1*03 and preceding Campylobacter jejuni infection (Pc = 0.05).

Radiologic and pathologic findings of intracerebral schwannoma.

We report the radiologic and pathologic findings of an intracerebral schwannoma. MR imaging studies showed a superficially located cystic mass with an enhancing nodule and evidence of peritumoral edema or gliosis.

Rheumatoid arthritis and cryptogenic organising pneumonitis.

We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.

Spontaneous bilateral carotid and vertebral artery dissection presenting as a Collet-Sicard syndrome.

Spontaneous dissection of the internal carotid arteries usually presents with unilateral headache, neck pain, focal ipsilateral cerebral ischaemic symptoms and a Horner's syndrome. Lower cranial nerve palsies are only rarely observed. We report a case of carotid and vertebral dissections presenting as a unilateral palsy of the ninth to twelfth cranial nerves (Collet-Sicard syndrome).

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.

Induced right-to-left cardiac shunt during pulmonary perfusion imaging.

Ventilation-perfusion lung scans are routinely performed using Tc-99m labeled MAA particles administered intravenously which are subsequently trapped in the pulmonary artery capillary bed. In the presence of a right-to-left shunt, activity may be seen in the systemic circulation. Right-to-left shunts may be worsened by inducing hypoxemia which causes pulmonary artery constriction, and also by increasing venous return to the heart. In this case, the authors used various maneuvers to increase right-to-left shunting and thereby demonstrated the presence of fixed pulmonary hypertension. These findings suggested that the patient's dyspnea on exertion was not primarily because of left ventricular dysfunction, and proposed coronary bypass surgery was deferred for medical management.

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.

Clinical and epidemiologic features of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is defined clinically as a peripheral neuropathy causing limb weakness that progresses for up to 4 weeks before reaching a plateau. The symptoms may be caused by inflammatory demyelination, axonal degeneration, or both. GBS occurs throughout the world, with a median incidence of 1.3 cases/100,000 population (range, 0.4-4.0). Males are more commonly affected than females, and there are peaks in young adults and the elderly. There is no clear seasonal association in Western countries, although this may be because the most frequent antecedent events, respiratory and enteric infections, have opposite seasonality. The most frequently identified cause of GBS is Campylobacter jejuni infection, which has been identified in up to 41% of patients and is associated with more severe disease and prolonged disability. Summer epidemics of GBS occur among children and young adults in Northern China and are particularly likely to be associated with C. jejuni infection.

Guillain-Barré syndrome.

Guillain-Barré syndrome has now become recognized as a clinical syndrome that may be due to several pathological entities, consisting of an acute inflammatory demyelinating polyradiculoneuropathy as well as an acute motor axonal neuropathy. Campylobacter jejuni infection is a common preceding event and, together with anti-ganglioside GM1 antibodies, is associated with axonal damage and a poor outcome. The mechanism by which such antibodies damage axons is not clear. The Miller Fisher syndrome is very closely associated with antibodies to ganglioside GQ1b that may be important in pathogenesis. Treatment of Guillain-Barré syndrome with intravenous immunoglobulin appears to be as effective as plasma exchange in one controlled trial. Two small series have reported a high incidence of early relapses following intravenous immunoglobulin, and its efficacy is being reexamined in a further controlled trial.

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.

Two pregnant women with vomiting and fits.

Two women with hyperemesis gravidarum were first seen with a short history of confusion diplopia, unsteadiness, and fits caused by Wernicke's encephalopathy. The neurologic presentation had been precipitated by a carbohydrate load inadvertently administered without vitamin supplementation. We stress the importance of prescribing thiamine supplements to all women with prolonged vomiting during pregnancy.

Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection.

To clarify the association between Campylobacter jejuni (Cj) infection and antibodies to ganglioside GM1 (anti-GM1) in Guillain-Barré syndrome (GBS), we have carried out a prospective case-control study of 96 patients with GBS. Cj infection occurred in 25 (26%) patients. IgG and/or IgM anti-GM1 were identified in 24 (25%) patients and in 1 of 71 (1.4%) household controls (p < 0.001). Thirteen of the 25 (52%) Cj-positive patients had anti-GM1 compared with 11 of the 71 (15%) Cj-negative patients (p < 0.001). Neither the peak overall disability nor the 1-year disability differed between the anti-GM1-positive and anti-GM1-negative patients. However, patients with the combination of Cj infection and anti-GM1 positivity recovered more slowly than Cj/anti-GM1-negative patients (p = 0.05), were more likely to have axonal degeneration, and were significantly more disabled at the end of 1 year (p = 0.02). The presence of Cj infection is more important than anti-GM1 positivity in determining the extent of axonal involvement and, hence, prognosis. Since the presence of anti-GM1 is not a significant poor-prognostic factor, a search should be made for other properties of Cj infection that would account for its relationship to axonal degeneration.

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).