Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive functioning.

The aim of this longitudinal cohort study, is to provide more insight into the pattern of brain abnormalities, and possible consequences for cognitive functioning, in patients with classic infantile Pompe disease. We included 19 classic infantile Pompe patients (median age last assessment 8.9 years, range 1.5-22.5 years; 5/19 CRIM negative), treated with ERT. Using MR imaging of the brain (T1, T2, and FLAIR acquisitions), we classified progression of brain abnormalities on a 12-point rating scale at multiple time points throughout follow-up. Additionally we noted specific white matter patterns and examined atrophy. Cognitive development was studied using Wechsler IQ assessments obtained by certified neuropsychologists. The association between age and cognitive functioning, and MRI ratings and cognitive functioning was assessed by linear regression models. All but one patient developed brain abnormalities. The abnormalities progressed in a similar pattern throughout the brain, with early involvement of periventricular white matter, later followed by subcortical white matter, gray matter structures, and juxtacortical U-fibers. We found a significant decline (p < 0.01), with increasing age for full scale IQ, performance IQ and processing speed, but not for verbal IQ (p = 0.17). Each point increment in the 12-point MRI rating scale was associated with a significant decline (3.1-6.0 points) in all the IQ index scores (p < 0.05). The majority of long-term surviving patients in our cohort develop incremental brain MRI abnormalities and decline in cognitive functioning. This highlights the need for new therapies that can cross the blood-brain barrier in order to treat this CNS phenotype.

Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Carboxyhaemoglobin levels in infants with hypoxic ischaemic encephalopathy.

OBJECTIVES: Hypoxic ischaemic encephalopathy (HIE) is associated with oxidative stress. A potential marker of oxidative damage is carboxyhaemoglobin (COHb) which is the product of the reaction between carbon monoxide and haemoglobin and is routinely assessed on blood gas analysis. Our objective was to test the hypothesis that higher COHb levels would be associated with worse outcomes in infants treated for HIE. METHODS: A retrospective, observational study was performed of all infants who received whole body hypothermia for HIE at a tertiary neonatal intensive care unit between January 2018 and August 2021. For each participating infant, the highest COHb level per day was recorded for days one, three and five after birth. RESULTS: During the study period, 67 infants with a median (IQR) gestational age of 40 (38-41) weeks underwent therapeutic hypothermia for HIE. The median (IQR) COHb level on day three was higher in infants without electroencephalographic seizures (1.4 [1.1-1.4] %) compared with infants with seizures (1.1 [0.9-1.3] %, p=0.024). The median (IQR) COHb on day five was higher in infants without MRI brain abnormalities (1.4 [1.2-1.7] %) compared with infants with MRI abnormalities (1.2 [1.0-1.4] %, p=0.032). The COHb level was not significantly different between the nine infants who died compared to the infants who survived. CONCLUSIONS: COHb levels were higher in infants with HIE without seizures and in those with normal MRI brain examinations. We suggest that carbon monoxide has a potential protective role in HIE.

Is the brain involved in patients with late-onset Pompe disease?

Our objective was to investigate brain structure, cerebral vasculature, and cognitive function in a cohort of patients with late-onset Pompe disease, with particular reference to the differences from those with the classic infantile phenotype, where extensive white-matter abnormalities (WMA) and impaired cognition on long-term enzyme treatment are reported in a subset of patients. Brain imaging (T1, T2, T2 fluid-attenuated inversion recovery, susceptibility-weighted images, and magnetic resonance angiography-time of flight) was combined with extensive cognitive testing of general intelligence (Wechsler IQ Test, Montreal Cognitive Assessment [MoCA]) and specific neuropsychological domains (verbal fluency, cognitive flexibility, attention, memory, and visuospatial abilities). We included 19 patients with late-onset Pompe disease (age range 11-56 years). Two patients showed mild punctate WMA within normal range for age, with a Fazekas score (FS) of 1 to 2. Magnetic resonance angiography revealed a slight vertebrobasilar dolichoectasia in two patients yet did not show any aneurysms or vascular dissections. Most patients had age-adjusted scores within the normal range for the Wechsler index scores (verbal comprehension, perceptual reasoning, working memory, and processing speed) and combined total intelligence (IQ) score (median 101, interquartile range 91-111; one patient had a below-average score for total IQ) as well as for the specific domains verbal fluency, attention, and memory. A subset of patients performed suboptimally on the Rey Complex Figure Test (9/14 patients) or cube-copying/clock-drawing test of the MoCA (8/10 patients). We therefore concluded that our study showed no brain abnormalities, other than minor microvascular lesions considered within normal range for age, nor general cognitive impairment in late-onset Pompe patients. These findings are in sharp contrast with the widespread WMA and cognitive problems found in some classic infantile patients.

Deep Reinforcement Learning with Automated Label Extraction from Clinical Reports Accurately Classifies 3D MRI Brain Volumes.

Image classification is probably the most fundamental task in radiology artificial intelligence. To reduce the burden of acquiring and labeling data sets, we employed a two-pronged strategy. We automatically extracted labels from radiology reports in Part 1. In Part 2, we used the labels to train a data-efficient reinforcement learning (RL) classifier. We applied the approach to a small set of patient images and radiology reports from our institution. For Part 1, we trained sentence-BERT (SBERT) on 90 radiology reports. In Part 2, we used the labels from the trained SBERT to train an RL-based classifier. We trained the classifier on a training set of [Formula: see text] images. We tested on a separate collection of [Formula: see text] images. For comparison, we also trained and tested a supervised deep learning (SDL) classification network on the same set of training and testing images using the same labels. Part 1: The trained SBERT model improved from 82 to [Formula: see text] accuracy. Part 2: Using Part 1's computed labels, SDL quickly overfitted the small training set. Whereas SDL showed the worst possible testing set accuracy of 50%, RL achieved [Formula: see text] testing set accuracy, with a [Formula: see text]-value of [Formula: see text]. We have shown the proof-of-principle application of automated label extraction from radiological reports. Additionally, we have built on prior work applying RL to classification using these labels, extending from 2D slices to entire 3D image volumes. RL has again demonstrated a remarkable ability to train effectively, in a generalized manner, and based on small training sets.

Brain morphometric changes in patients with fibromyalgia.

The aim of this study was to determine whether there is a decrease or an increase in the volume of different regions of the brain by comparing brain morphometry ofpatients diagnosed with Fibromyalgia Syndrome and healthy control subjects. The study included 23 female patients who were diagnosed with fibromyalgia, and 18 females, age-matched healthy subjects. Structural Mitral Regurgitation data was processed using Surface-Based Morphometry (SBM) on the Freesurfer 6.0 programme (http://surfer.nmr.mgh.harvard.edu). As a result of the surface-based analyses, a statistically significant reduction was determined in the Fibromyalgia Syndrome patient group in some brain region. A statistically signficant increase was determined in the FMS patient group with respect to the left anterior occipital sulcus volume, left inferior temporal gyrus thickness and left anterior occipital sulcus area. The results of this study showed that FMS affected brain morphometry through the brain central pain mechanisms and the normal brain morphology was changed because of atrophy in some areas and hypertrophy in some areas.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Bringing psychiatrists into the picture: Automated measurement of regional MRI brain volume in patients with suspected dementia.

OBJECTIVE: The volumes of various brain regions can be rapidly quantified using automated magnetic resonance imaging tools. While these appear to be useful at face value, their formal clinical utility is not yet understood, particularly for non-neuroradiologists and in patients presenting with suspected dementia. This study investigated the utility of an automated normative morphometry tool on determinations of brain atrophy by psychiatrists and radiologists in a tertiary hospital. METHODS: Consecutive magnetic resonance scans (n = 110) of patients referred with suspected neurodegenerative disorders were obtained retrospectively and rated by two neuroradiologists, two general radiologists and four psychiatrists over two sessions. First, conventional magnetic resonance sequences were shown. Then, morphometry colour-coded maps, which segmented T1-weighted magnetisation prepared rapid gradient echo images into brain regions and visualised these regions in colour according to their volumetric standard deviation from a normative population, were added to the second reading which occurred ⩾6 weeks later. Presence and laterality of atrophy in frontal, parietal and temporal lobes and hippocampal regions were measured using a digital checklist. The primary outcome of inter-rater agreement on atrophy was measured with Fleiss' Kappa (κ). We also evaluated the accuracy of the atrophy ratings for differentiating post hoc diagnosis of subjective cognitive impairment, mild cognitive impairment and dementia. RESULTS: Agreement among all raters was fair in frontal lobe and moderate in other regions with conventional method (κ = 0.362-0.555). With morphometry, higher agreement was seen in all regions (κ = 0.551-0.654), reaching significant improvement in the frontal and temporal lobes. No significant improvement was seen within the various disciplines, except in frontal lobes rated by psychiatrists. Accuracy of atrophy ratings on determining post hoc diagnosis was significantly improved for distinguishing subjective cognitive impairment versus dementia. CONCLUSION: In routine clinical assessment, automated normative morphometry complements the determination of regional atrophy and improves inter-rater agreement regardless of neuroradiology experience.

CADASIL: yesterday, today, tomorrow.

BACKGROUND AND PURPOSE: In 2019, the Brain Prize crowned the discovery of CADASIL in the 1990s and research efforts on this archetypal small vessel disease of the brain over 40 years. METHODS AND RESULTS: The hereditary origin of this arteriolopathy was discovered from a first clinical case and detailed observation of the patient's family. Thereafter, the role of causative mutations within the NOTCH3 gene were identified, allowing the development of a genetic test and then of an animal model of the disease. These crucial steps led to the discovery progressively that CADASIL is the most common genetic cerebral small vessel disease, to describing for the first time the natural history of a cerebral ischaemic small vessel disease from silent cerebral tissue lesions up to severe motor disability and dementia at the end stage, to demonstrating the central role of matrix proteins in its pathophysiology and to opening the door to the discovery of several other genes involved in monogenic cerebral small vessel diseases. DISCUSSION: Today, CADASIL is known to every neurologist, but the disease has not yet revealed all its secrets. A lot of effort is still needed to understand the intimate mechanisms of the disease and the most efficient targets or approaches for the development of efficient therapeutics. The history of CADASIL will be further enriched by multiple ongoing research projects worldwide, at clinical and preclinical level, and will continue to enlighten research in the field of cerebral small vessel disorders.

Transient contrast induced neurotoxicity after coronary angiography: A contrast re-challenge case.

Contrast induced neurotoxicity (CIN) is a rare complication of cardiac catheterization and re-exposure to contrast medium carries the risk of recurrent CIN. We report a case of successful contrast re-challenge in a 60-year-old female patient who developed CIN after her first procedure of coronary angiography (CAG) which resulted in symptoms of disorientation, amnesia and cortical blindness. A non-contrast enhanced CT performed four hours after the CAG was normal, however, her MRI brain scan showed scattered tiny hyper intensities in posterior occipito-temporal and parietal regions suggesting CIN. Patient's symptoms resolved completely after 72 hours. Two months later, because of persistent exertional angina, patient was successfully re-challenged with lesser amount of contrast medium with administration of hydrocortisone prior to procedure, and PCI to LAD was completed without recurrence of CIN.

Associations of Neonatal Noncardiac Surgery with Brain Structure and Neurodevelopment: A Prospective Case-Control Study.

OBJECTIVE: To examine the associations of neonatal noncardiac surgery with newborn brain structure and neurodevelopment at 2 years of age. STUDY DESIGN: Infants requiring neonatal noncardiac surgery for congenital diaphragmatic hernia, esophageal atresia, or anterior abdominal wall defect were compared with infants who did not require surgery, matched for sex, gestation at birth, and postmenstrual age at magnetic resonance imaging. Cerebral magnetic resonance imaging was performed at a mean (SD) postmenstrual age of 41.6 (1.7) weeks. Images were assessed qualitatively for brain maturation and injury and quantitatively for measures of brain size, cerebrospinal fluid spaces, and global abnormality. Neurodevelopment was then assessed at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd edition. RESULTS: Infants requiring surgery (n = 39) were 5.9 times (95% CI, 1.9-19.5; P < .01) more likely to have delayed gyral maturation and 9.8 times (95% CI, 1.2-446; P = .01) more likely to have white matter signal abnormalities compared with controls (n = 39). Cases were more likely to have higher global abnormality scores, smaller biparietal diameters, and larger ventricular sizes than controls. Infants who had surgery had lower mean composite scores in the language (mean difference, -12.5; 95% CI, -22.4 to -2.7) and motor domains (mean difference, -13.4; 95% CI, -21.1 to -5.6) compared with controls. CONCLUSIONS: Infants requiring neonatal noncardiac surgery have smaller brains with more abnormalities compared with matched controls and have associated neurodevelopmental impairment at 2 years of age. Prospective studies with preoperative and postoperative imaging would assist in determining the timing of brain injury.

Cognitive behavioural impairment with irreversible sensorineural deafness as a complication of West Nile encephalitis.

Despite common clinical features to suggest encephalitis, different viral encephalitides are known to have some specific clinical features, which if present, may suggest infection by a particular virus. West Nile viral (WNV) encephalitis has not been described with any specific diagnostic feature so far. In this context, we describe three patients of West Nile encephalitis (WNE) who had behavioural and cognitive impairment with acute irreversible bilaterally symmetrical sensorineural deafness. Clinical profiles of these cases suggest that the patients who present with prominent behavioural and cognitive changes and have in addition features of bilateral sensorineural deafness may be considered as the possible case of WNE.

Brain Tumor Detection and Segmentation by Intensity Adjustment.

In recent years, Brain tumor detection and segmentation has created an interest on research areas. The process of identifying and segmenting brain tumor is a very tedious and time consuming task, since human physique has anatomical structure naturally. Magnetic Resonance Image (MRI) scan analysis is a powerful tool that makes effective detection of the abnormal tissues from the brain. Among different techniques, Magnetic Resonance Image (MRI) is a liable one which contains several modalities in scanning the images captured from interior structure of human brain. A novel hybrid energy-efficient method is proposed for automatic tumor detection and segmentation. The proposed system follows K-means clustering, integrated with Fuzzy C-Means (KMFCM) and active contour by level set for tumor segmentation. An effective segmentation, edge detection and intensity enhancement can detect brain tumor easily. For that, active contour with level set method has been utilized. The performance of the proposed approach has been evaluated in terms of white pixels, black pixels, tumor detected area, and the processing time. This technique can deal with a higher number of segmentation problem and minimum execution time by ensuring segmentation quality. Additionally, tumor area length in vertical and horizontal positions is determined to measure sensitivity, specificity, accuracy, and similarity index values. Further, tumor volume is computed. Knowledge of the information of tumor is helpful for the physicians for effective diagnosing in tumor for treatments. The entire experimentation was implemented in MATLAB environment and simulation results were compared with existing approaches.

Chained regularization for identifying brain patterns specific to HIV infection.

Human Immunodeficiency Virus (HIV) infection continues to have major adverse public health and clinical consequences despite the effectiveness of combination Antiretroviral Therapy (cART) in reducing HIV viral load and improving immune function. As successfully treated individuals with HIV infection age, their cognition declines faster than reported for normal aging. This phenomenon underlines the importance of improving long-term care, which requires a better understanding of the impact of HIV on the brain. In this paper, automated identification of patients and brain regions affected by HIV infection are modeled as a classification problem, whose solution is determined in two steps within our proposed Chained-Regularization framework. The first step focuses on selecting the HIV pattern (i.e., the most informative constellation of brain region measurements for distinguishing HIV infected subjects from healthy controls) by constraining the search for the optimal parameter setting of the classifier via group sparsity (ℓ2,1-norm). The second step improves classification accuracy by constraining the parameterization with respect to the selected measurements and the Euclidean regularization (ℓ2-norm). When applied to the cortical and subcortical structural Magnetic Resonance Images (MRI) measurements of 65 controls and 65 HIV infected individuals, this approach is more accurate in distinguishing the two cohorts than more common models. Finally, the brain regions of the identified HIV pattern concur with the HIV literature that uses traditional group analysis models.

Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient.

WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.

Role of ADC values and ratios of MRI scan in differentiating typical from atypical/anaplastic meningiomas.

Atypical/anaplastic meningiomas are prone to aggressive behaviour which affects treatment planning and prognostication. Our aim was to assess the role of Apparent Diffusion Coefficient (ADC) values of MRI brain in differentiating typical from atypical/anaplastic meningioma. We reviewed 84 typical and 37 atypical/anaplastic meningiomas and compared mean ADC values and ADC ratios of their preoperative MRI brain. At 3 Tesla, mean ADC value for typical meningioma was1.03±0.10x10-3 and 0.63±0.05x10-3 for atypical/anaplastic meningioma. At 1.5 Tesla, mean ADC value for typical meningioma was 1.05±0.11x10-3 and atypical/ anaplastic meningioma was 0.70 ± 0.04x10-3. The mean ADC ratios were 1.08 ± 0.17 and 0.85 ± 0.15 for typical and atypical/anaplastic meningomas respectively. Mean ADC ratios and the mean ADC values of typical and atypical/anaplastic meningiomas were significantly different (p< 0.001). ADC values and ADC ratios have important role in differentiating typical from atypical/anaplastic meningioma and it must be part of the routine preoperative MRI reporting.

Nelarabine-induced peripheral and central neurotoxicity: can sequential MRI brain imaging help to define its natural history?

A 14-year-old boy with relapsed T cell acute lymphoblastic leukaemia received reinduction chemotherapy that included nelarabine, a purine nucleoside analogue known to cause dose-dependent neurotoxicity. Although he achieved aminimal residual disease negative remission after two cycles of chemotherapy he also developed severe, progressive peripheral and central neurotoxicities. Loss of grey-white differentiation was seen on a T2-weighted magnetic resonance imaging brain scan. This unusual clinical picture and previously unreported radiological findings are thought to be due to nelarabine toxicity. He was bridged with 6-mercaptopurine while transplant was deferred pending sustainable neurological improvement. This case posed clinical and ethical dilemmas while demonstrating previously unreported radiological features.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Image Retrieval Based on Local Mesh Vector Co-occurrence Pattern for Medical Diagnosis from MRI Brain Images.

In modern health-care, for evidence-based diagnosis, there is a requirement for an efficient image retrieval approach to retrieve the cases of interest that have similar characteristics from the large image databases. This paper presents a feature extraction approach that aims at extracting texture features present in the medical images using Local Pattern Descriptor (LPD) and Gray-level Co-occurrence Matrix (GLCM). As a main contribution, a novel local pattern named Local Mesh Vector Co-occurrence Pattern (LMVCoP) has been proposed by concatenating the Local Mesh Co-occurrence Pattern (LMCoP) and the Local Vector Co-occurrence Pattern (LVCoP). The fusion of GLCM with the Local Mesh Pattern (LMeP) and the Local Vector Pattern (LVP) produces LMCoP and LVCoP respectively. The LMVCoP method has been investigated on the Open Access Series of Imaging Studies (OASIS): a Magnetic Resonance Imaging (MRI) brain image database. LMVCoP descriptor achieves 87.57% of ARP and 53.21% of ARR which are higher than the existing methods of LTCoP, PVEP, LBDP, LMeP and LVP. The LMVCoP method enhances the retrieval results of LMeP/LVP from 81.36%/83.52% to 87.57% in terms of ARP on OASIS MRI brain database.

Spontaneous upper eyelid ecchymosis: A rare presenting sign for frontal sinus mucocele.

Paranasal sinus mucoceles are benign lesions that commonly present with orbital signs due to their anatomic proximity. We are reporting a case of bilateral frontal sinus mucocele presenting with spontaneous eyelid ecchymosis. To our knowledge this is the first case report of eyelid ecchymosis as the initial sign of this condition. In addition, our patient lacked commonly described symptoms such as diplopia or pain. This report highlights the importance of including frontal sinus mucocele in the differential diagnosis of spontaneous periorbital ecchymosis.