The authors declare no conflicts of interest.

Dear Editor, We would like to report a novel finding on standard diffusion-weighted magnetic resonance imaging (DWI-MRI) in a case series of four patients with giant cell arteritis (GCA) in the superficial temporal artery (STA). GCA is considered a clinical emergency and is the most common vasculitis in adults, which, if untreated, can rapidly cause irreversible sight loss and ischaemic stroke [1]. Unfortunately, clinical presentation is variable and classic symptoms such as headache and scalp tenderness can be absent, delaying diagnosis and therapy [1]. Temporal artery biopsy (TAB) is considered the reference standard for diagnosis, but sensitivity can be as low as 40% due to skip lesions and inadequate specimens [2]. The European Alliance of Associations for Rheumatology recommends temporal and axillary artery ultrasound (US) as a first-line investigation in patients suspected of having GCA [3]. The finding of an arterial halo on US, reflecting inflammatory oedema of the arterial wall, is thought diagnostic for GCA with a specificity of 96% [4]. However, the sensitivity of US is lower (43–77%) and is highly technique and operator dependent [4, 5]. In both TAB and US, sensitivity drops further if performed after commencing steroid therapy. Post-contrast vessel wall magnetic resonance imaging (VW-MRI) has been proposed as a potential alternative first-line imaging investigation, with experienced units reporting a sensitivity of 80% and a specificity of 100% [5]. VW-MRI is still a relatively new technique and not yet readily available.

Background. The underlying mechanisms of papilledema associated with intracranial hypertension remain unclear. A case of bilateral papillary edema in a patient with chronic idiopathic intracranial hypertension who was asymptomatic during her two pregnancies is reported. Case Presentation. A 19-year-old Caucasian female, in her third month of pregnancy, complained of difficulties with close reading. The patient’s visual acuity was 20/20 on the Snellen chart and improved with a 0.50 D correction in both eyes. Near vision and slit lamp examinations revealed normal findings bilaterally. However, a fundus examination showed bilateral papillary edema without evidence of hemorrhages or neovascularization. Blood tests were unremarkable, except for a slight increase in C-reactive protein levels. The patient had a prepregnancy weight of 63 kilograms, with a BMI of 24.91 kg/m2. Magnetic resonance imaging of the brain revealed features consistent with chronic idiopathic intracranial hypertension, which resolved after delivery. Two and a half years later, during a subsequent pregnancy, the patient experienced a recurrence of bilateral papillary edema due to the IIH. It was managed similarly as the first occurrence, resulting in bilateral anatomical and functional recovery. Recent research revealed that, during pregnancy, hormones interact with the central nervous system, leading to an increase in the size of neurons which could potentially result in intracranial hypertension. Conclusions. The influence of hormonal fluctuations during pregnancy on the development of transient central nervous system abnormalities in individuals with chronic intracranial hypertension, leading to papillary edema, remains a matter of debate.

AIM:To identify imaging predictors of molecular subtype and tumour grade in patients with isocitrate dehydrogenase (IDH) gene mutant (IDHmut) World Health Organization (WHO) grade 2 or 3 gliomas.MATERIALS AND METHODS:Patients with histologically confirmed WHO grade 2 or 3 IDHmut gliomas between 2016 and 2019 were included in the study. Magnetic resonance imaging (MRI) images were evaluated for the presence or absence of potential imaging predictors of tumour subtype, such as T2/fluid attenuated inversion recovery (FLAIR) signal match, and these factors were examined using regression analysis. On perfusion imaging, the maximum relative cerebral blood volume (rCBVmax) was evaluated as a potential predictor of tumour grade. The performance of two experienced neuroradiologists in correctly predicting tumour type on MRI was evaluated.RESULTS:Eighty-five patients were included in the study. The presence of T2/FLAIR signal match >50% of tumour volume (p<0.01) and intratumoural susceptibility (p=0.02) were independent predictors of 1p/19q co-deletion. Mean rCBV max was significantly higher in WHO grade 3 astrocytomas (p=0.04) than WHO grade 2 astrocytomas. The consensus prediction of 1p/19q co-deletion status by two neuroradiologists of tumour was 95% sensitive and 86% specific.CONCLUSION:The presence of matched T2/FLAIR signal could be used to identify tumour subtype when biopsy is inconclusive or genetic analysis is unavailable. rCBVmax predicted astrocytoma grade. Experienced neuroradiologists predict tumour subtype with good sensitivity and specificity.

Context: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. Design, Setting, and Patients: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Main Outcome Measures: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Results: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P=.007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P=.011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P=.023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Conclusion: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Background Cerebral microhaemorrhages are increasingly being recognised as a complication of COVID-19. This observational retrospective study aims to further investigate the potential pathophysiology through assessing the pattern of microhaemorrhage and clinical characteristics of patients with COVID-19 and microhaemorrhage. By comparing with similar patterns of microhaemorrhage in other non-COVID-19 disease, this study aims to propose possible common pathogenic mechanisms. Methods A retrospective observational case series was performed identifying all patients with COVID-19 complicated by cerebral microhaemorrhage on MRI. The distribution and number of microhaemorrhages were recorded using the microbleed anatomical scale, and patients' baseline characteristics and salient test results were also recorded. Results Cerebral microhaemorrhages were noted to have a predilection for the corpus callosum, the juxtacortical white matter and brainstem. All patients had a preceding period of critical illness with respiratory failure and severe hypoxia necessitating intubation and mechanical ventilation. Discussion This study demonstrates a pattern of cerebral microhaemorrhage that is similar to the pattern reported in patients with non-COVID-19 related critical illness and other causes of severe hypoxia. This raises questions regarding whether microhaemorrhage occurs from endothelial dysfunction due the direct effect of SARS-CoV-2 infection or from the secondary effects of critical illness and hypoxia.

Objective To describe a novel case of coronavirus disease 2019 (COVID-19)-associated acute necrotizing encephalopathy (ANE) in a patient with aplastic anemia where there was early brain stem-predominant involvement. Methods Evaluation of cause, clinical symptoms, and treatment response. Results A 59-year-old woman with a background of transfusion-dependent aplastic anemia presented with seizures and reduced level of consciousness 10 days after the onset of subjective fever, cough, and headache. Nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) was positive, and CT during admission demonstrated diffuse swelling of the brain stem. She required intubation and mechanical ventilation for airway protection, given her reduced level of consciousness. The patient's condition deteriorated, and MRI on day 6 demonstrated worsening brain stem swelling with symmetrical hemorrhagic lesions in the brain stem, amygdalae, putamina, and thalamic nuclei. Appearances were consistent with hemorrhagic ANE with early brain stem involvement. The patient showed no response to steroid therapy and died on the eighth day of admission. Conclusions COVID-19 may be associated with an acute severe encephalopathy and, in this case, was considered most likely to represent an immune-mediated phenomenon. As the pandemic continues, we anticipate that the spectrum of neurologic presentation will broaden. It will be important to delineate the full clinical range of emergent COVID-19-related neurologic disease.

Sickle cell disease is the most common hereditary hemoglobinopathy, which results in abnormally shaped and rigid red blood cells. These sickle-shaped red blood cells cause vaso-occlusion and ischemic phenomena that can affect any organ in the body. As a common cause of disability, the neurological manifestations of sickle cell disease are particularly important. Neuroimaging has a crucial role in the diagnosis, management, and prevention of the complications of sickle cell disease. These complications can affect the brain parenchyma, vasculature, and skull and can be ascribed directly or indirectly to a vasculopathy of small and large vessels. Vaso-occlusion can cause ischemic stroke. Ischemic damage in the absence of an acute neurological deficit, and therefore only apparent on neuroimaging, is termed silent cerebral ischemia. Weakening of the arterial walls can cause aneurysms. In its most severe form, a vasculopathy of the terminal internal carotid arteries can progress to moyamoya syndrome, characterized by steno-occlusive disease and the formation of friable collateral arteries. Rupture of aneurysms or friable collateral arteries is a potential cause of intracranial hemorrhage. The skull and vertebrae may be affected by extra-medullary hematopoiesis, due to severe anemia, or iron deposition, due to chronic red blood cell transfusion. Impaired blood supply to bone is associated with osteomyelitis and osteonecrosis. Fat embolization syndrome is a rare complication of osteonecrosis, which may cause devastating neurological impairment. Awareness and early recognition of the diverse manifestations of sickle cell disease on neuroimaging is crucial to ensure optimal treatment in a complex patient cohort.

Background: Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI). Objective: The aim of this study was to investigate possible alterations, and their clinical relevance, in neurite morphology along the brain and cervical spinal cord of relapsing–remitting MS (RRMS) patients. Methods: In total, 28 RRMS patients and 20 healthy controls (HCs) underwent brain and spinal cord NODDI at 3T. Physical and cognitive disability was assessed. Individual maps of orientation dispersion index (ODI) and neurite density index (NDI) in brain and spinal cord were obtained. We examined differences in NODDI measures between groups and the relationships between NODDI metrics and clinical scores using linear regression models adjusted for age, sex and brain tissue volumes or cord cross-sectional area (CSA). Results: Patients showed lower NDI in the brain normal-appearing white matter (WM) and spinal cord WM than HCs. In patients, a lower NDI in the spinal cord WM was associated with higher disability. Conclusion: Reduced neurite density occurs in the neuraxis but, especially when affecting the spinal cord, it may represent a mechanism of disability in MS.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objective The objective of this study was to investigate the contrast-to-noise ratio (CNR) between cortical gray matter (GM) and subcortical white matter (WM) across the cortex in relation to the ability of 3-dimensional fluid attenuated inversion recovery and 3-dimensional double inversion recovery to distinguish between cortical lesions (CLs) and juxtacortical lesions (JCs). Methods A total of 38 multiple sclerosis patients underwent magnetic resonance imaging. Two neuroradiologists scored CLs and JCs on magnetic resonance imaging in 9 cerebral areas. Lesions were marked as nonclassifiable (NCs) when blurred WM-GM boundary leads to inaccuracy of their discrimination. The CNR between WM and GM (CNRWM-GM) was evaluated across the cortical areas. Results The CNRWM-GM varies across the cortex; the lower values were found in motor and sensorimotor areas where almost all NCs were localized. A strong negative correlation was found between CNRWM-GM and NCs. Conclusions Discrimination between CLs and JCs is affected from the sharp visualization of the WM-GM boundary, which is directly related to CNRWM-GM.

On the basis of recent functional MRI studies, Multiple Sclerosis (MS) has been interpreted as a multisystem disconnection syndrome. Compared to normal subjects, MS patients show alterations in functional connectivity (FC). However, the mechanisms underlying these alterations are still debated. The aim of the study is to investigate resting state (RS) FC changes after initial treatment with fingolimod, a proven anti-inflammatory and immunomodulating agent for MS. We studied 32 right-handed relapsing-remitting MS patients (median Expanded Disability Status Scale: 2.0, mean disease duration: 8.8 years) who underwent both functional and conventional MRI with a 3 Tesla magnet. All assessments were performed 3 weeks before starting fingolimod, then, at therapy-initiation stage and at month 6. Each imaging session included scans at baseline (run1) and after (run2) a 25-min, within-session, motor-practice task, consisting of a paced right-thumb flexion. FC was assessed using a seed on the left primary motor cortex to obtain parametric maps at run1 and task-induced FC change (run2-run1). Comparison between 3-week before- and fingolimod start sessions accounted for a test-retest effect. The main outcome was the changes in both baseline and task-induced changes in FC, between initiation and 6 months. MRI contrast enhancement was detected in 14 patients at initiation and only in 3 at month 6. There was a significant improvement (p < 0.05) in cognitive function, as measured by the Paced Auditory Serial Addition Task, at month 6 compared to initiation. After accounting for test-retest effect, baseline FC significantly decreased at month 6, with respect to initiation (p < 0.05, family-wise error corrected) in bilateral occipito-parietal areas and cerebellum. A task-induced change in FC at month 6 showed a significant increment in all examined sessions, involving not only areas of the sensorimotor network, but also posterior cortical areas (cuneus and precuneus) and areas of the prefrontal and temporal cortices (p < 0.05, family-wise error corrected). Cognitive improvement at month 6 was significantly (p < 0.05) related to baseline FC reduction in posterior cortical areas. This study shows significant changes in functional connectivity, both at baseline and after the execution of a simple motor task following 6 months of fingolimod therapy.

Aim: To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).Methods: We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software.Results: Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS.Conclusions: Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS. (C) 2017 Elsevier Ltd. All rights reserved.

Purpose To prospectively investigate, by using resting-state functional magnetic resonance (MR) imaging, cerebellar dentate nuclei (DNs) functional connectivity abnormalities in multiple sclerosis (MS) to explore their impact on balance impairment in patients with MS, considering the role of DNs and their projections in maintaining balance, posture, and muscle tone, Materials and Methods All subjects provided written informed consent, and the protocol was approved by the university institutional review board. Twenty-five patients with relapsing-remitting MS and 20 healthy control subjects underwent a 3-T resting-state functional MR imaging and static posturography. The seed-based method was applied to identify the cerebellar DNs resting-state network; first-level and high-level analyses were performed by using software tools. Results Compared with control subjects, patients had worse postural stability and altered patterns of cerebellar DNs connectivity network, with decreased connectivity in caudate nuclei and thalami and increased connectivity in the cerebellum, pons, left amygdala, and orbitofrontal cortices (cluster level, family-wise error corrected, P < .05, z threshold > 2.3). In patients, the decreased connectivity in the left caudate nucleus was related with worse balance performance (cluster level, family-wise error corrected P < .05, z threshold > 1.96) regardless of age, lesion burden, and global clinical disability. Conclusion These results reveal abnormalities of corticocerebellar circuit connectivity in patients with MS as compared with control subjects and suggest that the decreased connectivity between the DN and the left caudate nucleus could play a role in balance impairment in MS. © RSNA, 2017.

Background Pathological and MRI-based evidence suggests that multiple brain structures are likely to be involved in functional disconnection between brain areas. Few studies have investigated resting-state functional connectivity (rsFC) in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In this study, we investigated within- and between-network rsFC abnormalities in these two conditions. Methods Twenty patients with PSP, 11 patients with CBS, and 16 healthy subjects (HS) underwent a resting-state fMRI study. Resting-state networks (RSNs) were extracted to evaluate within- and between-network rsFC using the Melodic and FSLNets software packages. Results Increased within-network rsFC was observed in both PSP and CBS patients, with a larger number of RSNs being involved in CBS. Within-network cerebellar rsFC positively correlated with mini-mental state examination scores in patients with PSP. Compared to healthy volunteers, PSP and CBS patients exhibit reduced functional connectivity between the lateral visual and auditory RSNs, with PSP patients additionally showing lower functional connectivity between the cerebellar and insular RSNs. Moreover, rsFC between the salience and executive-control RSNs was increased in patients with CBS compared to HS. Conclusion This study provides evidence of functional brain reorganization in both PSP and CBS. Increased within-network rsFC could represent a higher degree of synchronization in damaged brain areas, while between-network rsFC abnormalities may mainly reflect degeneration of long-range white matter fibers.

Purpose To investigate thalamic connectivity changes after use of a video game-based cognitive rehabilitation program, as thalamic damage and alterations in thalamocortical functional connectivity (FC) are important factors in cognitive dysfunction in patients with multiple sclerosis (MS). Materials and Methods This prospective study was approved by the local ethical committee. Twenty-four patients with MS and cognitive impairment were randomly assigned to either an intervention or a wait-list group. Patients were evaluated with cognitive tests and 3-T resting-state functional magnetic resonance (MR) imaging at baseline and after an 8-week period. In addition, 11 healthy subjects underwent baseline resting-state functional MR imaging. Patients in the intervention group performed the video game-based cognitive rehabilitation program, while those in the wait-list group served as control subjects. Repeated measures analysis of variance was used to test efficacy of the intervention. The thalamic resting-state network was identified with a seed-based method; both first-level and high-level analyses were performed by using software tools. Results Patients showed lower baseline FC compared with healthy subjects. A significant improvement was seen in results of the Paced Auditory Serial Addition Test and the Stroop Test after 8 weeks of cognitive rehabilitation (F = 6.616, [P = .018] and F = 5.325 [P = .030], respectively). At follow-up, the intervention group had an increased FC in the cingulum, precuneus, and bilateral parietal cortex and a lower FC in the cerebellum and in left prefrontal cortex compared with the wait-list group (P < .05, family-wise error corrected); correlations were found between FC changes in these regions and cognitive improvement (P < .05, family-wise error corrected). Conclusion The results of this study show the relevance of thalamic regulation of the brain networks involved in cognition and suggest that changes in thalamic resting-state network connectivity may represent a functional substrate for cognitive improvement associated with a video game-based cognitive rehabilitation program. (©) RSNA, 2016.