Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis.

INTRODUCTION: Ixekizumab is an anti-interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date. CASE REPORT: A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion. CONCLUSION: This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti-IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.

Imaging features of rhinocerebral mucormycosis: from onset to vascular complications.

Rhinocerebral mucormycosis (RCM) may result in severe intracranial ischemic and hemorrhagic lesions. Both computed tomography (CT) and magnetic resonance imaging (MRI) play an essential role in the diagnosis of RCM, but whereas CT is better for assessing bone erosion, MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion. Specific CT and MRI techniques, such as CT angiography or enhanced MR angiography, and more advanced MRI sequences such as gadolinium-3D Black Blood imaging, contribute to the assessment of the extension of vascular invasion.In this pictorial review, we describe specific CT and MRI signs of RCM, mainly focusing on its life-threatening complications due to vascular involvement.

Isolated cerebellar progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation: focus on imaging.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is caused by JC virus opportunistic infection in the setting of immunodeficiency. Typical imaging features are multifocal and asymmetric lesions within supratentorial subcortical white matter in parieto-occipital regions. CASE DESCRIPTION: A 47-year-old patient experienced a relapse of acute myeloid leukemia 21 months after hematopoietic stem cell transplantation. He also had visual impairment and magnetic resonance imaging showed an isolated cerebellar lesion without mass effect or enhancement. Common opportunistic infections and leukemic central nervous system involvement were excluded by cerebrospinal fluid (CSF) analysis. Given the worsening clinical and radiologic scenario, PML was suspected, and CSF protein chain reaction analysis was positive for JC virus. CONCLUSIONS: Given its potential curability, PML should be thoroughly investigated in patients with hematologic neoplasms and atypical isolated cerebellar presentation.

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals.

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.

Brain miliary enhancement.

PURPOSE: Miliary enhancement refers to the presence of multiple small, monomorphic, enhancing foci on T1-weighted post-contrast MRI images. In the absence of a clear clinical presentation, a broad differential diagnosis may result in invasive procedures and possibly brain biopsy for diagnostic purposes. METHODS: An extensive review of the literature is provided for diseases that may present with miliary enhancement on T1-weighted brain MR images. Additional disease-specific findings, both clinical and radiological, are summarized and categorized by the presence or absence of perivascular space involvement. RESULTS: Miliary pattern of enhancement may be due to a variety of underlying causes, including inflammatory, infectious, nutritional or neoplastic processes. The recognition of disease spread along the perivascular spaces in addition to the detection or exclusion of disease-specific features on MRI images, such as leptomeningeal enhancement, presence of haemorrhagic lesions, spinal cord involvement and specific localisation or systemic involvement, allows to narrow the potential differential diagnoses. CONCLUSION: A systematic approach to disease-specific findings from both clinical and radiological perspectives might facilitate diagnostic work-up, and recognition of disease spread along the perivascular spaces may help narrowing down differential diagnoses and may help to minimize the use of invasive diagnostic procedures.

High-Resolution CT Change over Time in Patients with Idiopathic Pulmonary Fibrosis on Antifibrotic Treatment.

Antifibrotic treatment slows down functional decline and disease progression in idiopathic pulmonary fibrosis (IPF). High-resolution computed tomography (HRCT) is useful to diagnose IPF; however, little is known about whether and to what extent HRCT changes reflect functional changes during antifibrotic therapy. The aim of this study was, therefore, to assess HRCT change over time after 1 year of treatment and to evaluate whether these changes correlate with functional decline over the same period of time. Sixty-eight IPF patients on antifibrotic treatment (i.e., pirfenidone or nintedanib) were functionally categorized as stable or progressors based on whether (or not) they had a decline in forced vital capacity (FVC) >5% predicted/year, and their HRCT were scored blindly and independently by two expert thoracic radiologists at treatment initiation (HRCT1) and after 1 year of treatment (HRCT2). Ground glass opacities (Alveolar Score, AS), reticulations (Interstitial Score, IS) and honeycombing (HC) were quantified and correlated with FVC decline between HRCT1 and HRCT2. At treatment initiation, HRCT scores were similar in both stable patients and progressors. After one year of treatment, in the entire population, AS and HC increased significantly, while IS did not. However, when stratified by the rate of functional decline, in stable patients, HC increased significantly while AS and IS did not. On the other hand, among progressors AS and HC increased significantly whereas IS did not. In the entire population, the combined score of fibrosis (IS + HC) correlated significantly with FVC decline. In conclusion, IPF patients on antifibrotic treatment exhibit different patterns of HRCT change over time based on their rate of functional decline. HRCT data should be integrated to lung function data when assessing response to antifibrotic treatment in patients with IPF.

Temozolomide cytoreductive treatment in a giant cabergoline-resistant prolactin-secreting pituitary neuroendocrine tumor.

Dopamine agonists (DAs, especially cabergoline) are recommended as first-line treatment in patients with prolactin-secreting pituitary adenomas, to reduce hormone secretion and tumor size. Pituitary surgery, suggested in nonresponsive patients, cannot achieve a gross total resection or is not feasible in some cases. Temozolomide (TMZ) has been proposed in patients with aggressive pituitary neuroendocrine tumors (PitNETs) who do not respond to conventional treatments. We present a 47-year-old man with a giant (70×51×64 mm) prolactin-secreting PitNET. Cabergoline treatment (at first 1.5 mg/week, and then increased to 3.5 mg/week after 3 months) achieved prolactin suppression; however, magnetic resonance revealed a stable mass. After explanation of surgical complications, the patient rejected the procedure. Therefore, a primary neoadjuvant cytoreductive TMZ treatment was discussed during a meeting of the Pituitary Multidisciplinary Team, and added to cabergoline. After 13 cycles of TMZ (1 year of treatment), we observed dramatic reduction of the PitNET (from 18 cm of adenoma to 6 cm of necrotic tissue). MRI performed 4, 12, and 18 months after TMZ discontinuation revealed a stable residual PitNET, and 1.5 mg/week of cabergoline has been continued until today. Recently, the criteria for developing Pituitary Tumors Centers of Excellence have been proposed, indicating that a multidisciplinary team is the best care for patients. Surgery, rejected by the patient, could only achieve a partial resection; therefore, we decided to combine TMZ and cabergoline. An early initiation of TMZ could be considered in selected cases, especially when surgery could be only partially effective.

Accuracy of deep learning to differentiate the histopathological grading of meningiomas on MR images: A preliminary study.

BACKGROUND: Grading of meningiomas is important in the choice of the most effective treatment for each patient. PURPOSE: To determine the diagnostic accuracy of a deep convolutional neural network (DCNN) in the differentiation of the histopathological grading of meningiomas from MR images. STUDY TYPE: Retrospective. POPULATION: In all, 117 meningioma-affected patients, 79 World Health Organization [WHO] Grade I, 32 WHO Grade II, and 6 WHO Grade III. FIELD STRENGTH/SEQUENCE: 1.5 T, 3.0 T postcontrast enhanced T1 W (PCT1 W), apparent diffusion coefficient (ADC) maps (b values of 0, 500, and 1000 s/mm2 ). ASSESSMENT: WHO Grade II and WHO Grade III meningiomas were considered a single category. The diagnostic accuracy of the pretrained Inception-V3 and AlexNet DCNNs was tested on ADC maps and PCT1 W images separately. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to asses DCNN performance. STATISTICAL TEST: Leave-one-out cross-validation. RESULTS: The application of the Inception-V3 DCNN on ADC maps provided the best diagnostic accuracy results, with an AUC of 0.94 (95% confidence interval [CI], 0.88-0.98). Remarkably, only 1/38 WHO Grade II-III and 7/79 WHO Grade I lesions were misclassified by this model. The application of AlexNet on ADC maps had a low discriminating accuracy, with an AUC of 0.68 (95% CI, 0.59-0.76) and a high misclassification rate on both WHO Grade I and WHO Grade II-III cases. The discriminating accuracy of both DCNNs on postcontrast T1 W images was low, with Inception-V3 displaying an AUC of 0.68 (95% CI, 0.59-0.76) and AlexNet displaying an AUC of 0.55 (95% CI, 0.45-0.64). DATA CONCLUSION: DCNNs can accurately discriminate between benign and atypical/anaplastic meningiomas from ADC maps but not from PCT1 W images. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1152-1159.

A venous thromboembolism risk assessment model for patients with Cushing's syndrome.

Cushing's syndrome (CS) is associated with an incidence of venous thromboembolism (VTE) about ten times higher than in the normal population. The aim of our study was to develop a model for identifying CS patients at higher risk of VTE. We considered clinical, hormonal, and coagulation data from 176 active CS patients and used a forward stepwise logistic multivariate regression analysis to select the major independent risk factors for thrombosis. The risk of VTE was calculated as a 'CS-VTE score' from the sum of points of present risk factors. VTE developed in 20 patients (4 pulmonary embolism). The group of CS patients with VTE were older (p < 0.001) and had more cardiovascular events (p < 0.05), infections and reduced mobility (both p < 0.001), higher midnight plasma cortisol levels (p < 0.05), and shorter APTT (p < 0.01) than those without. We identified six major independent risk factors for VTE: age ≥69 years and reduced mobility were given two points each, whereas acute severe infections, previous cardiovascular events, midnight plasma cortisol level >3.15 times the normality and shortened APTT were given one point each. A CS-VTE score <2 anticipated no risk of VTE; a CS-VTE score of two mild risk (10 %); a CS-VTE score of three moderate risk (46 %); a CS-VTE score ≥4 high risk (85 %). Considering a score ≥3 as predictive of VTE, 94 % of the patients were correctly classified. A simple score helps stratify the VTE risk in CS patients and identify those who could benefit from thromboprophylaxis.

Perioperative thromboprophylaxis in Cushing's disease: What we did and what we are doing?

PURPOSE: Cushing's disease (CD) is associated with an increased risk of thrombotic events, particularly after surgery. No guidelines are available on the management of patients with CD undergoing pituitary transsphenoidal surgery (TSS). We aimed to compare the effectiveness of different prophylactic procedures on the prevention of thrombotic events after surgery in CD. METHODS: We retrospectively collected data on 78 consecutive patients who underwent TSS for CD between 2001 and 2012 at Padova's Neurosurgical Unit, recording their hemostatic, hormonal and anthropometric parameters. Patients were divided into two groups according to their perioperative management. Group A (34 patients) received fractionated heparin for a maximum of 14 days after surgery. Patients in group B (44 patients) were given no early glucocorticoid replacement therapy, and treated with subcutaneous enoxaparin 4,000-8,000 U/daily (depending on their weight) for 30 days plus graduated elastic stockings until mobilization, and early ambulation. RESULTS: The whole cohort of patients had clotting and anticoagulant factors significantly higher than the normal range. The two groups were comparable for age, BMI, ACTH, urinary free cortisol levels, outcome of surgery, and main clotting parameters. The surgical procedure did not change during the study period. Three venous thrombotic events [venous thromboembolic events (VTE), 2 associated with pulmonary embolism] were recorded in group A, none in group B (p = 0.079). No hemorrhagic events were reported. CONCLUSIONS: Provoked thrombotic events pose a major problem in the management of CD patients after surgery, regardless of the procedure's outcome. The prophylactic regimen proposed in this paper afforded an efficacy prophylaxis against postoperative VTE in patients with CD. Due to the rarity of CD, a multicenter study on a larger sample of cases would be warranted in order to collect more thrombotic events.

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC-MS/MS method in routine clinical practice.

OBJECTIVE: The Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. SUBJECTS AND METHODS: The LC-MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission. RESULTS: UFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de novo CS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy. CONCLUSIONS: Our data suggest high diagnostic performance of UFF excretion measured using LC-MS/MS, in detecting de novo CS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS.

Diagnosis and complications of Cushing's disease: gender-related differences.

OBJECTIVE: Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female-to-male ratio of 3-8:1. The aim of this study was to evaluate gender-related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease. METHODS: We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values). RESULTS: We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0·001) and ACTH values (P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0·05), hypercoagulable state and osteoporosis at lumbar spine (P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures. CONCLUSIONS: Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties.