Validation of 3- and 5-point severity scales to assess ARIA-E.

Introduction: Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) offer the promise of disease modification and are emerging treatment options in Alzheimer's disease. Anti-Aβ mAbs require brain magnetic resonance imaging (MRI) examinations to detect anti-amyloid-induced amyloid-related imaging abnormalities (ARIA), important adverse drug reactions associated with some anti-Aβ mAbs currently available in the United States and in clinical development. We present a simple rating system for ARIA-edema (ARIA-E) that can assess severity on a 3- or 5-point scale based upon a single linear measurement of the largest area of lesion, and dissemination in space, termed the 3-point Severity Scale of ARIA-E (SSAE-3) and the 5-point Severity Scale of ARIA-E (SSAE-5), respectively.

Development, initial validation, and application of a visual read method for [F]MK-6240 tau PET.

Background: The positron emission tomography (PET) radiotracer [F]MK-6240 exhibits high specificity for neurofibrillary tangles (NFTs) of tau protein in Alzheimer's disease (AD), high sensitivity to medial temporal and neocortical NFTs, and low within-brain background. Objectives were to develop and validate a reproducible, clinically relevant visual read method supporting [F]MK-6240 use to identify and stage AD subjects versus non-AD and controls.

Methods: Five expert readers used their own methods to assess 30 scans of mixed diagnosis (47% cognitively normal, 23% mild cognitive impairment, 20% AD, 10% traumatic brain injury) and provided input regarding regional and global positivity, features influencing assessment, confidence, practicality, and clinical relevance.

Comparing ARIA-E severity scales and effects of treatment management thresholds.

Introduction: Amyloid-related imaging abnormalities-edema (ARIA-E) is associated with anti-amyloid beta monoclonal antibody treatment. ARIA-E severity may be assessed using the Barkhof Grand Total Scale (BGTS) or the 3- or 5-point Severity Scales of ARIA-E (SSAE-3/SSAE-5). We assessed inter- and intra-reader correlations between SSAE-3/5 and BGTS.

Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson's disease trial.

Background: Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson's disease (PD). Depending on the stage of progression, approximately 5-15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood.

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease.

Importance: The EMERGE and ENGAGE phase 3 randomized clinical trials of aducanumab provide a robust data set to characterize amyloid-related imaging abnormalities (ARIA) that occur with treatment with aducanumab, an amyloid-β (Aβ)-targeting monoclonal antibody, in patients with mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia.

Objective: To describe the radiographic and clinical characteristics of ARIA that occurred in EMERGE and ENGAGE.

Design, Setting, And Participants: Secondary analysis of data from the EMERGE and ENGAGE trials, which were 2 double-blind, placebo-controlled, parallel-group, phase 3 randomized clinical trials that compared low-dose and high-dose aducanumab treatment with placebo among participants at 348 sites across 20 countries.

Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease.

Introduction: Solanezumab, a humanized monoclonal antibody that binds soluble amyloid beta peptide, is being developed for treatment of Alzheimer's disease (AD).

Methods: Patients (n = 2042) with mild and moderate AD were randomized 1:1 to 400-mg solanezumab or placebo infusion every 4 weeks for 80 weeks and 1457 patients entered an open-label extension. Magnetic resonance imaging scans monitored for amyloid-related imaging abnormalities-edema/effusion (ARIA-E) and amyloid-related imaging abnormalities-hemorrhage/hemosiderin deposition.

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated.

Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis.

Background: Amyloid-related imaging abnormalities due to haemosiderin deposition (ARIA-H) occur in patients with mild to moderate dementia due to Alzheimer's disease (AD) and have been reported with increased incidence in clinical trials of amyloid-lowering therapies under development for AD.

Objective: Our objective was to explore the relationship between the incidences of ARIA-H during treatment with placebo and different doses of bapineuzumab, a humanised monoclonal antibody directed against amyloid β.

Methods: Two neuroradiologists independently reviewed 2572 GRE/T2* MRI sequences from 262 participants in two phase two clinical trials of bapineuzumab and an open-label extension study.

Rhomb- and bickerstaff encephalitis: two clinical phenotypes?

We report unusual cases of brainstem encephalitis in two young boys. Both presented with acute febrile illness, progressive encephalopathy, and marked cerebrospinal fluid pleocytosis. Case one shared some of the clinical features that have been seen in previously reported cases of brainstem encephalitis, such as ophthalmoplegia, ataxia, and progressive encephalopathy.

A two-level multimodality imaging Bayesian network approach for classification of partial epilepsy: preliminary data.

Background: Quantitative neuroimaging analyses have demonstrated gray and white matter abnormalities in group comparisons of different types of non-lesional partial epilepsy. It is unknown to what degree these type-specific patterns exist in individual patients and if they could be exploited for diagnostic purposes. In this study, a two-level multi-modality imaging Bayesian network approach is proposed that uses information about individual gray matter volume loss and white matter integrity to classify non-lesional temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial-temporal sclerosis and frontal lobe epilepsy (FLE).

Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis.

Background: Amyloid-related imaging abnormalities (ARIA) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a humanised monoclonal antibody against amyloid β. ARIA include MRI signal abnormalities suggestive of vasogenic oedema and sulcal effusions (ARIA-E) and microhaemorrhages and haemosiderin deposits (ARIA-H). Our aim was to investigate the incidence of ARIA during treatment with bapineuzumab, and evaluate associated risk factors.

Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer's disease study cohorts from phase 3 trials of semagacestat and solanezumab.

Background: Cerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood-brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).

Methods: Fluid-attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double-blind, placebo-controlled, phase 3 trials in patients with mild-to-moderate AD.

Intra-lacrimal gland cavernous hemangioma.

Orbital cavernous hemangioma usually has a typical clinical and imagery pattern. We present a patient with an enlarged lacrimal gland due to an intra-gland cavernous hemangioma.

Magnetic resonance imaging quality and volumes of brain structures from live and postmortem imaging of California sea lions with clinical signs of domoic acid toxicosis.

Our goal in this study was to compare magnetic resonance images and volumes of brain structures obtained alive versus postmortem of California sea lions Zalophus californianus exhibiting clinical signs of domoic acid (DA) toxicosis and those exhibiting normal behavior. Proton density-(PD) and T2-weighted images of postmortem-intact brains, up to 48 h after death, provided similar quality to images acquired from live sea lions. Volumes of gray matter (GM) and white matter (WM) of the cerebral hemispheres were similar to volumes calculated from images acquired when the sea lions were alive.

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis.

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI.

Fibrous dysplasia.

An atypical presentation of fibrous dysplasia with a very large cystic component is described. The MR pattern was not diagnostic.

11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study.

Background: Carbon-11-labelled Pittsburgh compound B ((11)C-PiB) PET is a marker of cortical fibrillar amyloid-beta load in vivo. We used (11)C-PiB PET to investigate whether bapineuzumab, a humanised anti-amyloid-beta monoclonal antibody, would reduce cortical fibrillar amyloid-beta load in patients with Alzheimer's disease.

Methods: Patients with mild-to-moderate Alzheimer's disease were randomly assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to three in three ascending dose groups (0.

Involvement of the thalamocortical network in TLE with and without mesiotemporal sclerosis.

Purpose: The thalamus plays an important role in seizure propagation in temporal lobe epilepsy (TLE). This study investigated how structural abnormalities in the focus, ipsilateral thalamus and extrafocal cortical structures relate to each other in TLE with mesiotemporal sclerosis (TLE-MTS) and without hippocampal sclerosis (TLE-no).

Methods: T₁ and high-resolution T₂ images were acquired on a 4T magnet in 29 controls, 15 TLE-MTS cases, and 14 TLE-no.

Age-related gray matter shrinkage in a treatment naïve actively drinking alcohol-dependent sample.

Background: We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol-dependent (TxN) men compared to nonalcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect. In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon.

Methods: In the current study, we examine cortical gray matter volumes in 18- to 50-year-old TxN (n = 84) versus age and gender comparable controls (n = 67).

Neuroanatomy and volumes of brain structures of a live California sea lion (Zalophus californianus) from magnetic resonance images.

The California sea lion (Zalophus californianus) has been a focal point for sensory, communication, cognition, and neurological disease studies in marine mammals. However, as a scientific community, we lack a noninvasive approach to investigate the anatomy and size of brain structures in this species and other free-ranging, live marine mammals. In this article, we provide the first anatomically labeled, magnetic resonance imaging-based atlas derived from a live marine mammal, the California sea lion.

Parietal gray matter volume loss is related to spatial processing deficits in long-term abstinent alcoholic men.

Background: We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle-aged long-term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) (Fein et al., 2006).

Methods: In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results--i.

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: preliminary results.

Purpose: High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis.