Confabulation: damage to a specific inferior medial prefrontal system

Confabulation, the pathological production of false memories, occurs following a variety of aetiologies involving the frontal lobes, and is frequently held to be underpinned by combined memory and executive deficits. However, the critical frontal regions and specific cognitive deficits involved are unclear. Studies in amnesic patients have associated confabulation with damage to the orbital and ventromedial prefrontal cortex. However neuroimaging studies have associated memory control processes which are assumed to underlie confabulation with the right lateral prefrontal cortex. We used a confabulation battery to investigate the occurrence and localisation of confabulation in an unselected series of 38 patients with focal frontal lesions. 12 patients with posterior lesions and 50 healthy controls were included for comparison. Significantly higher levels of confabulation were found in the Frontal group, confirming previous reports. More detailed grouping according to lesion location within the frontal lobe revealed that patients with orbital, medial and left lateral damage confabulated in response to questions probing personal episodic memory. Patients with orbital, medial and right lateral damage confabulated in response to questions probing orientation to time. Performance-led analysis revealed that all patients who produced a total number of confabulations outside the normal range had a lesion affecting either the orbital region or inferior portion of the anterior cingulate. These data provide striking evidence that the critical deficit for confabulation has its anatomical location in the inferior medial frontal lobe. Performance on tests of memory and executive functioning showed considerable variability. Although a degree of memory impairment does seem necessary, performance on traditional executive tests is less helpful in explaining confabulation

Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known

Multiparameter MR Imaging in the 6-OPRI

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

Automated quantitative MRI volumetry reports support diagnostic interpretation in dementia: a multi-rater, clinical accuracy study

Objectives: We examined whether providing a quantitative report (QReport) of regional brain volumes improves radiologists’ accuracy and confidence in detecting volume loss, and in differentiating Alzheimer’s disease (AD) and frontotemporal dementia (FTD), compared with visual assessment alone. Methods: Our forced-choice multi-rater clinical accuracy study used MRI from 16 AD patients, 14 FTD patients, and 15 healthy controls; age range 52–81. Our QReport was presented to raters with regional grey matter volumes plotted as percentiles against data from a normative population (n = 461). Nine raters with varying radiological experience (3 each: consultants, registrars, ‘non-clinical image analysts’) assessed each case twice (with and without the QReport). Raters were blinded to clinical and demographic information; they classified scans as ‘normal’ or ‘abnormal’ and if ‘abnormal’ as ‘AD’ or ‘FTD’. Results: The QReport improved sensitivity for detecting volume loss and AD across all raters combined (p = 0.015* and p = 0.002*, respectively). Only the consultant group’s accuracy increased significantly when using the QReport (p = 0.02*). Overall, raters’ agreement (Cohen’s κ) with the ‘gold standard’ was not significantly affected by the QReport; only the consultant group improved significantly (κs 0.41➔0.55, p = 0.04*). Cronbach’s alpha for interrater agreement improved from 0.886 to 0.925, corresponding to an improvement from ‘good’ to ‘excellent’. Conclusion: Our QReport referencing single-subject results to normative data alongside visual assessment improved sensitivity, accuracy, and interrater agreement for detecting volume loss. The QReport was most effective in the consultants, suggesting that experience is needed to fully benefit from the additional information provided by quantitative analyses. Key Points: • The use of quantitative report alongside routine visual MRI assessment improves sensitivity and accuracy for detecting volume loss and AD vs visual assessment alone. • Consultant neuroradiologists’ assessment accuracy and agreement (kappa scores) significantly improved with the use of quantitative atrophy reports. • First multi-rater radiological clinical evaluation of visual quantitative MRI atrophy report for use as a diagnostic aid in dementia

Comparison of MR pulse sequences in the detection of multiple sclerosis lesions

PURPOSE: To compare the sensitivity of conventional spin-echo, fast spin-echo, fast fluid-attenuated inversion recovery (FLAIR), and turbo gradient spin-echo MR sequences in the detection of multiple sclerosis lesions. METHODS: Conventional spin-echo, fast spin-echo, fast FLAIR, and turbo gradient spin-echo sequences were performed on a 1.0-T MR imager in seven patients with clinically definite multiple sclerosis. The images in each sequence were evaluated by two raters and consensus was reached by agreement. RESULTS: In comparing conventional spin-echo with fast spin-echo sequences, five lesions were seen only by conventional spin-echo and 63 were seen only by fast spin-echo; in comparing conventional spin-echo with fast FLAIR sequences, 18 lesions were seen only by conventional spin-echo and 109 only by fast FLAIR; in comparing conventional spin-echo with turbo gradient spin-echo sequences, 51 lesions were seen only by conventional spin-echo and seven only by turbo gradient spin-echo; in comparing fast spin-echo with fast FLAIR sequences, 45 lesions were seen only by fast spin-echo and 52 only by fast FLAIR. CONCLUSION: Fast spin-echo and fast FLAIR sequences improve the sensitivity of MR imaging in the detection of multiple sclerosis lesions with reduced acquisition time as compared with conventional spin-echo sequences. These sequences should therefore be considered for serial studies in patients with multiple sclerosis. The sensitivity of turbo gradient spin-echo was inferior to the other sequences, but its reduced acquisition time could make this technique the ideal choice for patients who cannot tolerate longer examination times

Intraobserver and interobserver variability in measuring changes in lesion volume on serial brain MR images in multiple sclerosis

PURPOSE: We evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis. METHODS: Eighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique. RESULTS: Lesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION: Our data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis

Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis

PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2- weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections