Neuroimaging of CNS infection in haematological malignancy: important signs and common diagnostic pitfalls.

Patients with haematological malignancy are at increased risk of developing central nervous system (CNS) infections, which are associated with significant morbidity and mortality. Neuroimaging plays a pivotal role in the diagnostic pathway of these patients; however, layers of complexity are added to image interpretation by the heterogeneity in imaging manifestations of haematological malignancies in the CNS, overlapping imaging features of CNS infection, treatment-related parenchymal changes and the presence of intracranial comorbidity. In this article, we review important intracranial findings of CNS infection cases accrued in 1,855 studies over more than a decade at a specialist tertiary centre. We offer schema to identify common and important neuroimaging features, discuss key differential diagnoses and frequent diagnostic pitfalls.

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.

Extensive subclinical sinusitis leading to Moraxella osloensis meningitis.

We report a case of a 31 year old male with extensive subclinical sinusitis leading to erosion in the cribriform plate and subsequent meningitis caused by the organism Moraxella osloensis. The patient presented to the emergency department with rapid onset confusion, neck stiffness and headache. Inflammatory markers, renal and liver function, and a chest radiograph were all normal. CT Head showed extensive polyp disease in the paranasal sinuses with expansion of the left frontal sinus and CT Sinuses revealed an area of low attenuation in the cribriform plate consistent with bony erosion. MRI Head showed thick loculated sinus inflammation. Lumbar puncture yielded CSF with a high white cell count of predominantly mononuclear cells, no visible organisms and an elevated protein. CSF microscopy, culture and viral PCR were not diagnostic, and so the CSF was sent for 16S rDNA PCR screening, which identified the rDNA of Moraxella osloensis. Moraxella osloensis is a rare cause of bacterial meningitis, with only a few reported cases. This case illustrates that sinusitis, while a common condition, when severe can predispose to intracranial infection with atypical and low virulence organisms such as Moraxella species, which do not commonly cause invasive CNS disease. This case represents the first case of Moraxella osloensis meningitis reported from the United Kingdom.

Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation.

BACKGROUND: The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. METHOD: The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.

Brain-water diffusion coefficients reflect the severity of inherited prion disease.

OBJECTIVE: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. METHODS: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. RESULTS: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). CONCLUSIONS: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases.

High-b-value diffusion MR imaging and basal nuclei apparent diffusion coefficient measurements in variant and sporadic Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: DWI using a standard b-value of 1000 s/mm(2) has emerged as the most sensitive sequence for the diagnosis of CJD. The purpose of this study was to investigate whether DWI at a high b-value (b = 3000 s/mm(2)) and ADC measurements in the basal nuclei improve the diagnosis of vCJD and sCJD compared with visual assessment of DWI at a standard b-value (b = 1000 s/mm(2)). MATERIALS AND METHODS: Eight patients with vCJD, 9 patients with sCJD, and 5 healthy volunteers underwent DWI at b = 1000 s/mm(2), and 5 vCJD patients, 4 sCJD patients, and 1 growth hormone-related CJD patient underwent DWI at b = 3000 s/mm(2). Two consultant neuroradiologists performed a visual comparison of the b = 1000 and b = 3000 images. Mean MR SI and ADC values were determined for C, P, and DM thalamus ROIs bilaterally at each b-value. SI ratios for each ROI relative to white matter were calculated. RESULTS: In 9 out of 10 patients, the higher b-value images were more sensitive to SI change, particularly in cortex and thalamus, with higher SI ratios at b = 3000 in the DM thalamus. For sCJD at b = 1000, we found significantly lower ADC values in the C and P compared with controls (mean C ADC = 587.3 +/- 84.7 mm(2)/s in sCJD patients versus 722.7 +/- 16.6 mm(2)/s in controls; P = .007), and at b = 3000, the differences were more pronounced. In comparison, in vCJD at b = 1000, ADC values were elevated in the Pu (mean Pu ADC = 837.6 +/- 33.0 mm/s(2) in vCJD patients versus 748.0 +/- 17.3 mm/s(2) in controls; P < .001) but failed to reach significance at b = 3000. CONCLUSIONS: Our results demonstrate that b = 3000 DWI, being more sensitive to slowly diffusing tissue water, is more sensitive to pathology in sCJD than is conventional DWI. High-b-value DWI increases confidence in the radiologic diagnosis of human prion disease.

Neuroimaging of CNS involvement in HIV.

Central nervous system involvement in HIV-positive patients is common with 40% of patients suffering neurological disease at some point in their lives. Neuroimaging is important to properly diagnose treatable conditions and to monitor response to treatment. In this article, we describe and illustrate the main CNS imaging findings. The following categories of pathology are addressed: direct neurological effects of HIV, opportunistic CNS infections and neoplasms, cerebrovascular complications of HIV and CNS effects of highly active retroviral therapy (HAART). Imaging techniques employed include computed tomography, magnetic resonance imaging, diffusion-weighted imaging, functional magnetic resonance imaging and magnetic resonance spectroscopy.

Magnetic resonance imaging and spectroscopy of the brain in HIV disease.

Severe AIDS dementia complex is now a rare clinical condition in resource-rich settings in HIV-1-infected patients with access to modern antiretroviral therapies. However, minor neurocognitive decline and central nervous system abnormalities have been reported in clinical studies assessing HIV-1-infected subjects on modern antiretroviral therapy with undetectable plasma HIV-RNA. Ongoing characterisation and monitoring of these abnormalities are crucial to aid our understanding and assess future interventions. New magnetic resonance imaging (MRI) techniques, provide a non-invasive mechanism to assess impaired brain function (functional MRI, fMRI) and detect changes in brain biochemistry (magnetic resonance spectroscopy, MRS). In this review, changes described by fMRI and MRS in HIV disease both in the pre- and post-combination antiretroviral therapy eras are summarised.

The imaging features of post-traumatic myositis ossificans, with emphasis on MRI.

Post-traumatic myositis ossificans is a benign condition of heterotopic bone formation, which can mimic soft-tissue and bone malignancies. This pictorial review describes the specific imaging features of myositis ossificans using different imaging techniques, but with emphasis on MRI.

Selective attention to food-related stimuli in hunger: are attentional biases specific to emotional and psychopathological states, or are they also found in normal drive states?

Previous work has indicated that anxiety disorders and eating disorders are associated with selective processing of stimuli relevant to patients' concerns (e.g. Mathews and MacLeod, 1994; Annual Review of Psychology, 45, 25-50; Channon et al., 1988; British Journal of Clinical Psychology, 27, 259-260). A dot probe task was used to investigate whether attentional biases are also a feature of a normal drive state. Specifically, we examined whether hunger is associated with biases in selective attention and in pre-attentive processes for food-relevant stimuli. Subjects with high levels of hunger showed a greater attentional bias for food-related words presented in a suprathreshold exposure condition (words shown for 500 msec), in comparison with those with low hunger. There was no evidence in the present study of a hunger-related bias in pre-attentive processes (i.e. when words were shown for 14 msec and masked). Results suggest that a non-emotional motivational state, such as hunger, is associated with a bias in certain aspects of information processing, such as selective attention, for stimuli that are relevant to the motivational state. Findings are discussed in relation to recent research into emotion-related cognitive biases.