Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma.

While non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.

Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities.

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p=0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p=0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

BACKGROUND AND PURPOSE: Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). METHODS: We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. RESULTS: About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P < 0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis. CONCLUSIONS: AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.

CT and MRI diagnosis of silent sinus syndrome.

PURPOSE: The purpose of this study was to determine computed tomography (CT) and magnetic resonance (MR) findings of silent sinus syndrome (SSS) - a rare clinical entity with the constellation of progressive enophthalmos and hypoglobus, facial asymmetry and possible diplopia - due to otherwise asymptomatic maxillary sinus disease. MATERIALS AND METHODS: We reviewed the pre- and postoperative CT and MR images of six patients with a definitive diagnosis of SSS and compared the radiological and clinical findings with those reported in the literature. RESULTS: The CT and MR studies demonstrated in all cases the most characteristic imaging features of SSS reported in the literature. CONCLUSIONS: Both CT and MR imaging enable a diagnosis of SSS to be made, but CT provides a better depiction of all features of SSS necessary for diagnosis and differentiation from other sinus conditions, even in patients without a clinical suspicion of SSS.

Magnetic resonance imaging of solitary brain metastases: main findings of nonmorphological sequences.

PURPOSE: This study was done to investigate the usefulness of diffusion-weighted (DWI), perfusion-weighted (PWI) and proton magnetic resonance (MR) spectroscopy imaging in characterising solitary brain metastases. MATERIALS AND METHODS: Fifty-nine solitary brain metastases were evaluated with conventional and nonmorphological MR imaging: DWI, PWI and MR spectroscopy. We evaluated size, signal intensity and contrast enhancement and calculated apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), percentage of signal intensity recovery (PSR) and maximum values of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipids (Lip), NAA/Cr and Cho/Cr. The nonmorphological parameters were compared with those from the literature for brain lesions that frequently enter the differential diagnosis with metastases. RESULTS: Signal intensity and contrast enhancement patterns were variable. There was a wide range of ADC values: min:max 0.59×10(-3):1.88×10(-3). Compared with normal white matter, rCBV was higher in lesions (3.30±1.59) and lower in perilesional oedema (0.42±0.15). Mean and minimum PSR were 57% and 48%, respectively; lip and Cho were elevated and NAA reduced. CONCLUSIONS: Conventional MR findings of solitary metastases are heterogeneous, and some values of nonmorphological sequences are similar to those of other brain lesions. PWI seems to be the nonmorphological MR technique that may best contribute to the diagnosis of brain metastases.

3D rotational angiography for the diagnosis and preoperative assessment of intracranial aneurysms: preliminary experience.

PURPOSE: The aim of this study was to assess the value of the systematic use of 3D rotational angiography (3DRA) in the diagnosis and preoperative evaluation of cerebral aneurysms with a view to planning endovascular embolisation. MATERIALS AND METHODS: Thirty-five consecutive aneurysms (20 incidental and 15 after subarachnoid haemorrhage) were studied and treated by means of 3DRA over a 1-year period. All rotational studies were conducted by selective cannulation of the vessel supplying the lesion (internal carotid artery or vertebral artery) with a single injection of 20 cc of contrast agent after diagnostic angiography in anterior-posterior (AP) and laterolateral (LL) views. Three-dimensional reconstructions were generated within a mean time of 5 min, and coil embolisation was performed on the basis of the 3D images. RESULTS: Three-dimensional RA enabled accurate definition of site, orientation, morphology and size of the sac and its relationship with the parent arteries and helped us choose the most appropriate angulation of the C-arm for guiding and controlling the embolisation procedure. Furthermore, the technique allowed us to detect six aneurysms for which conventional imaging had yielded equivocal results. CONCLUSIONS: Based on our experience before RA equipment became available and in agreement with the literature, we believe that 3DRA improves the identification of all lesions and helps refine the choice of the most suitable embolisation material and technique. Three-dimensional RA requires substantially fewer projections and thus reduces radiation dose and volume of contrast material to the patient. The use of 3DRA most likely results in a shorter procedure time and fewer risks and complications for the patient.

Immunity to extracellular matrix antigens is associated with ultrastructural alterations of the stroma and stratified epithelium basement membrane in the skin of Hashimotos thyroiditis patients.

Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and V collagens (CI, CIII, CIV, CV), laminin (LM) and fibronectin (FN), as antigen sources we detected autoantibodies to conformational and/or denatured ECM antigens among 34 of 50 sera obtained from Hashimotos thyroiditis (HT) patients and 6 of 51 control sera obtained from non-autoimmune thyroid disease patients and healthy donors (HT sera vs. control sera p=4 x 10-9). Reactivity to conformational antigens, mostly due to autoantibodies of the IgG isotype, was observed in 30/50 HT sera and in 6/51 control sera (p=3.5 x 10-7) and was not always concomitant with that to linear antigens, found in 23/50 HT and in 6/51 control sera (p=1.6 x 10-4). Ultrastructural analysis of skin biopsies obtained from 18 HT patients without symptomatic cutaneous diseases revealed defects of the stratified squamous epithelium basement membrane in 11/18, alterations of the stroma in 13/18 and both basement membrane and stromal defects in 9/18. Interestingly, 13/13 (p=0.012) and 9/11 (p=0.012) patients with stromal and basement membrane defects respectively, exhibited serum antibodies to at least one ECM antigen involved in the organization of the altered tissue compartment. Lastly, 10/18 skin biopsies presented immunoglobulin (Ig) and/or complement (C3) deposits along the cutaneous basement membrane zone (BMZ) or in the papillary dermis and 9/10 sera from the same patients simultaneously showed antibodies to at least one ECM antigen involved in the organization of these two skin compartments. Besides, 8/11 HT patients with basement membrane defects exhibited Ig or C3 deposits along the BMZ. Our findings suggest that autoantibodies to ECM molecules might contribute to the development of asymptomatic extra-thyroid skin diseases in HT patients.

NCAM is hyposialylated in hereditary inclusion body myopathy due to GNE mutations.

The authors found that the neural cell adhesion molecule (NCAM) is hyposialylated in hereditary inclusion body myopathy (HIBM) muscle, as suggested by its decreased molecular weight by Western blot. This abnormality represented the only pathologic feature differentiating HIBM due to GNE mutations from other myopathies with similar clinical and pathologic characteristics. If further confirmed in larger series of patients, this may be a useful diagnostic marker of GNE-related HIBM.

Metastatic lymphadenopathy from ENT carcinoma: role of diagnostic imaging.

Problems concerning the use of different imaging modalities in N staging of the neck are dealt with. The peculiar features, findings, sensitivity, specificity and diagnostic accuracy of each modality in the diagnosis of nature of cervical lymphadenopathy are described, as reported in most recent reports of literature, and according to the personal experience. CT/MRI criteria commonly used to establish whether a lymph node is metastatic or benign/reactive are related to the size, morphology, density (CT), signal intensity (MRI), evidence of central necrosis and extracapsular spread. Color Doppler US is a reliable method in the diagnosis of cervical metastatic lymphadenopathy even if no parameter is highly predictive; the combination of different findings, especially cortical thickening and structural inhomogeneity with thin, compressed, displaced or non visualized hilum makes the procedure significantly sensitive and specific. Intranodal hilar vascularization on color Doppler, with high resistance arterial flow (PI > 1.5), enhances the predictive value of findings of bi-dimensional sonography. Extracapsular spread impacts on survival as well as on the number of recurrences, which increases in patients with extracapsular spread; the disease-free interval is less in these patients. The identification and definition of extracapsular spread is based on some CT/MRI criteria as: 1) lymph nodes with spiky, irregular margins; 2) loss of adipose cleavage planes around the node and thickening of adjacent fascia; 3) apparent invasion of an adjacent structures or muscles. Similarly to CT/MR, sonographic findings of extracapsular spread can be: 1) blurred margins and irregular contours; 2) invasion of an adjacent structure or muscle.

Superior extension of intraoperative brain damage in case of normothermic systemic perfusion during coronary artery bypass operations.

OBJECTIVE: Despite the controversies on the potential detrimental effects of normothermic cardiopulmonary bypass on neurologic outcome, to date no correlation between the severity of intraoperative brain lesions and the cardiopulmonary bypass temperature used at operation has been reported. This study compares the prevalence and the severity of brain lesions in patients who underwent operation in condition of normothermic versus hypothermic systemic perfusion. METHODS: Data are derived from the analysis of 2987 consecutive primary isolated myocardial revascularizations performed at our institution between April 1990 and January 1997. Of these cases, 1385 procedures were hypothermic and 1602 procedures were normothermic systemic perfusion. In all cases the neurologic outcome and extent of ischemic areas were prospectively recorded. RESULTS: Overall, 31 patients had a perioperative stroke (1.0%). The prevalence of neurologic events was similar in the 2 groups (15 cases in the hypothermic group and 16 cases in the normothermic perfusion group; P, not significant). However, the mean Glasgow Outcome Scale score and computed tomography-demonstrated extent of brain lesions were significantly worse in the normothermic group. CONCLUSIONS: Although the prevalence of intraoperative stroke was similar with hypothermic or normothermic cardiopulmonary bypass, the use of normothermic systemic perfusion was associated with more extended brain damage at computed tomographic scan and with a worse neurologic outcome. These results demand caution in the use of normothermic cardiopulmonary bypass and claim further investigation on the neurologic safety of normothermia.

Modification of the Talairach stereotactic system for CT-compatibility: technical note.

A modification of the Talairach stereotactic system is described which is able to incorporate CT data and provides both co-ordinate calculations, directly from the CT console screen and by a fiducial reference system. The device maintains the original base plate, thus allowing its interfacing with all the accessories of the early apparatus and its direct use in the stereotactic operating room. The instrument has shown great reliability in the localisation of brain lesions and considerable flexibility in many stereotactic operations such as biopsy procedures, brachytherapy, radiosurgery and stereotactically assisted resections.

Diagnostic imaging of neurotuberculosis.

Neurotuberculosis is represented by different and possibly concomitant forms, of which the most frequent are tuberculous meningitis and parenchymal tuberculosis followed by cerebral miliary tuberculosis and the extremely rare tuberculous abscesses. Tuberculous meningitis is characterized by the presence of inflammatory meningeal exudate involving meningeal surfaces and CSF spaces with involvement of relative vascular and nervous structures. Most frequent complications are parenchymal infarction, hydrocephalus and mycotic aneurysms. Inflammatory meningeal exudate shows intense contrast enhancement. Parenchymal tuberculosis may directly involve the cerebral and/or medullary parenchyma as areas of cerebritis/myelitis with solid nodular lesions (tuberculomas) with a central area of caseating necrosis. Tuberculomas are characterized by intense nodular or ring enhancement.

Unilateral demodicidosis.

A 45-year-old man presented with a unilateral, papulopustular, rosacealike, chronic dermatitis which involved the left portion of the forehead and the eyelids unilaterally. Many Demodex mites were found in the follicles of the affected area. Topical crotamiton cleared the lesions after an unsuccessful trial with oral metronidazole. This observation provides further evidence that demodicidosis is a condition distinct from common rosacea.

Tumors of cerebral hemispheres.

Pediatric brain tumors are substantially represented by neuroepithelial neoplasms. If intraventricular tumors are excluded, diagnostic imaging can be referred to 3 main types: gliomas, neuronal and mixed tumors, embryonal tumors. Following a short review of the various neuroimaging procedures, CT and MRI findings of most common pediatric hemispheric neoplasms, are described. Neuroradiologic findings supply a satisfactory "characterization" of the neoplasm. They are at times so specific as to achieve a univocal diagnostic hypothesis. More frequently, only a likely histologic hypothesis is achieved based on the combination of neuroimaging and clinical findings. Finally, the role of diagnostic imaging is underlined, being important in the definition of the relationships between hemispheric tumors with some "critical" areas, because of "functional" relevance, and in the identification of the site and pattern of infiltration which impact on prognosis and treatment.