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In Anderson–Fabry disease (AFD) the impact of left ventricular (LV) function on cardiac outcome is unknown. Noninvasive LV pressure–strain loop analysis is a new echocardiographic method to estimate myocardial work (MW). We aimed to evaluate whether LV function was associated with outcome and whether MW had a prognostic value in AFD. Ninety-six AFD patients (41.8 ± 14.7 years, 43.7% males) with normal LV ejection fraction were retrospectively evaluated. Inclusion criteria were sinus rhythm and ≥ 2-year follow-up. Standard echocardiography measurements, myocardial mechano-energetic efficiency (MEE) index, global longitudinal strain (GLS) and MW were evaluated. Adverse cardiac events were defined as composite of cardiac death, malignant ventricular tachycardia, atrial fibrillation and severe heart failure development. During a median follow-up of 63 months (interquartile range 37–85), 14 events occurred. Patient age, cardiac biomarkers, LV mass index, left atrium volume, E/Ea ratio, LV ejection fraction, MEE index, GLS and all MW indices were significantly related to adverse outcome at univariate analysis. After adjustment for clinical and echocardiographic parameters, which were significant at univariate analysis, GLS and MW resulted independent predictors of adverse events (p

The appropriate surgical management of early-stage oral tongue squamous cell carcinoma (OTSCC) remains a debated topic. The aim of this study is to investigate the role of the pre-treatment neutrophil to lymphocyte ratio (NLR) and tumor depth of invasion (DOI) in predicting the presence of occult neck metastases in early-stage OTSCC. A retrospective analysis of patients affected by early-stage (cT1-T2 cN0) OTSCC who were submitted to elective neck dissection (END) was performed. Tumors were classified retrospectively according to the 8th TNM classification, the DOI was assessed on the pre-operative magnetic resonance imaging, and the pre-treatment NLR was calculated for each patient. A logistic regression model to estimate the probability π (x) of cervical metastases by studying the NLR and DOI was carried out. Next, the correlation between the two variables, the NLR and DOI, was preliminarily studied. A cohort of 110 patients was analyzed (mean age, 62 years old; male to female ratio 1.2:1). The patients were staged as cT1 in 53 cases and cT2 in 57 cases. A DOI greater than 5.4 mm and a NLR greater than 2.93 are associated with an increased risk of presenting occult cervical metastases. Furthermore, the variables NLR and DOI are linearly associated with a positive correlation, proved by Spearman's rank correlation coefficient rho of 0.64, with a unitary increase in the DOI of 1 mm directly associated with an increase of 0.47 in the NLR. The DOI and NLR can be effectively used to predict the occurrence of occult neck metastasis and therefore to plan an END in early-stage OTSCC.

Purpose Recent evidences have suggested the possible presence of an involvement of the extrapyramidal system in Fabry disease (FD), a rare X-linked lysosomal storage disorder. We aimed to investigate the microstructural integrity of the main tracts of the cortico-striatal-thalamo-cortical loop in FD patients. Methods Forty-seven FD patients (mean age = 42.3 ± 16.3 years, M/F = 28/21) and 49 healthy controls (mean age = 42.3 ± 13.1 years, M/F = 19/28) were enrolled in this study. Fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) maps were computed for each subject, and connectomes were built using a standard atlas. Diffusion metrics and connectomes were then combined to carry on a diffusion MRI tractometry analysis. The main afferent and efferent pathways of the cortico-striatal-thalamo-cortical loop (namely, bundles connecting the precentral gyrus (PreCG) with the striatum and the thalamus) were evaluated. Results We found the presence of a microstructural involvement of cortico-striatal-thalamo-cortical loop in FD patients, predominantly affecting the left side. In particular, we found significant lower mean FA values of the left cortico-striatal fibers (p = 0.001), coupled to higher MD (p = 0.001) and RD (p p = 0.01) and RD (p = 0.01) values at the level of the thalamo-cortical fibers. Conclusion We confirmed the presence of an alteration of the extrapyramidal system in FD patients, in line with recent evidences suggesting the presence of brain changes as a possible reflection of the subtle motor symptoms present in this condition. Our results suggest that, along with functional changes, microstructural damage of this pathway is also present in FD patients.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder affecting multiple systems, due to inactivating mutations of TSC1 or TSC2 mTOR pathway genes. Neurological manifestations are observed in about 95% cases, representing the most frequent cause of morbidity and one of the most common causes of mortality. Neuroimaging is crucial for early diagnosis, monitoring, and management of these patients. While computed tomography is generally used as first-line investigation at emergency department, magnetic resonance imaging is the reference method to define central nervous system involvement and investigate subtle pathophysiological alterations in TSC patients. Here, we review the state-of-the-art knowledge in TSC brain imaging, describing conventional findings and depicting the role of advanced techniques in providing new insights on the disease, also offering an overview on future perspectives of neuroimaging applications for a better understanding of disease pathophysiology.

Purpose Evaluation of clinical and radiological effects of the therapeutic outcome of CT-guided pulsed radiofrequency (PRF) treatment adjacent to the lumbar dorsal root ganglion (DRG) for patients with chronic intractable lumbosacral radicular pain in a single-center prospective longitudinal study in order to evaluate predictive factors of safety and therapeutic success. Materials and methods Thirty patients, from 2016 to 2018, were enrolled (age: 42–80 aa, 66.7% men and 33.3% females) with low back pain, lumbosciatalgia and/or lumbocruralgia, resistant to previous medical and physical treatments for a period not < 3 months, failure of surgical and chemiodiscolysis with ozone oxygen therapy. Each patient was subjected to a clinical evaluation (antalgic walking, sensitive deficit, interviews with specific questionnaires: ODI, RDQ,VAS) and to a radiological evaluation with MRI examination, before and 30 days after the CT-guided PRF treatment. Measurements of the thickness of the involved and not involved DRG were taken using common postprocessing software of MRI examinations in order to have measurement parameters for comparison. We analyzed the clinical course using the paired samples T test in order to evaluate modification for each clinical and radiological parameter (statistical significance p < 0.05). Results Significant improvements of the clinical outcomes with a good resolution of the pain symptoms (VAS evaluation: The score fell from 68.47 to 39.17 with a difference of 29.3 and a reduction of the 42.79% in the perceived pain, p = 0.00000152). The thickness of DRG falls from an average media of 0.586–0.448 cm (p = 0.000085), with a difference of 0.138 cm and a percentage reduction of 22.30%. Conclusions PRF treatment of the DRG may be considered for patients with chronic severe lumbosacral radicular pain refractory to conventional medical management when other noninvasive or surgical procedures fail. It is minimally invasive, inexpensive and simple to perform with no complications.

If Huntington disease (HD) may represent a risk factor for Covid-19 is debated. The aim of our work was to assess the impact of Covid-19 pandemic on HD disease progression, to evaluate patients vulnerability to Covid-19 infection and the incidence of severe manifestations compared to the general population. Methods After obtaining oral informed consent, we conducted a telephone interview directed to patients or care-givers, using an ad hoc developed semi-structured questionnaire. The questionnaire was composed of two sections and is shown in table 1. Section one: telephone interview to HD patients Section two: telephone interview to HD patients who tested positive for COVID19 Results We interviewed a total of 112 HD patients. Since the beginning of the pandemic, 72.3% of patients experienced a progression of the basal clinical condition (figure 1). Thirty-one-percent of patients changed their pre-existing psychiatric therapy or started a new one. Interestingly, 50% described the onset of a new sleep disorder. Analysis of the standards of care showed that 78% of the patients missed their scheduled medical visit and 64.7% stopped physiotherapy. Within the observed cohort 10.8% of patients tested positive for Covid-19 infection, 6 experienced symptoms and 5 of them had comorbidities. Despite resolution of the infection 3 patients underwent a rapid progressive and generalized clinical worsening. Conclusion Our study was among one of the first to investigate the impact of the Covid-19 pandemic on HD patients. Our results shown that most patients experienced a global clinical worsening since the beginning of the pandemic. Despite the more severe confinement measure adopted by HD patients, the incidence, and the morbidity of Covid-19 infection seemed to be higher than the general population (Buder, et al., 2021). Whether HD represents per se a risk factor for COVID-19 is unclear. However, a negative impact of HD on the immune system has been described, and difficulties in swallowing and clearing secretions may have negatively impacted the disease course.

Simple Summary Central nervous system involvement (CNS) is a common finding in Neurofibromatosis type 1 (NF1). Beside tumor-related manifestations, NF1 is also characterized by a wide spectrum of CNS alterations with variable impacts on functioning and life quality. Here, we propose an overview of non-oncological neuroradiological findings in NF1, with an insight on pathophysiological and embryological clues for a better understanding of the development of these specific alterations. Abstract Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is characterized by several manifestations that pervasively involve central and peripheral nervous system structures. The disorder is due to mutations in the NF1 gene, which encodes for the ubiquitous tumor suppressor protein neurofibromin; neurofibromin is highly expressed in neural crest derived tissues, where it plays a crucial role in regulating cell proliferation, differentiation, and structural organization. This review article aims to provide an overview on NF1 non-neoplastic manifestations of neuroradiological interest, involving both the central nervous system and spine. We also briefly review the most recent MRI functional findings in NF1.

Meningioangiomatosis is a rare congenital hamartomatous malformation of the leptomeninges that can also involve the adjacent cerebral tissue, sometime arising in association with neurofibromatosis. Here we report the case of a 55-year-old man with neuroradiological evidence of meningioangiomatosis, known to be a well-defined malformative-dysplastic lesion, preceding the onset of central nervous system B-cell lymphoma. We describe for the first time this unusual association, highlighting how meningioangiomatosis could accompany different pathologies more frequently than thought. Keywords: Meningioangiomatosis, Neurofibromatosis, Lymphoma, Magnetic resonance imaging

Introduction: Aim of this study is to elucidate possible mechanisms of extrapyramidal damage in Fabry Disease (FD), a condition in which involvement of the motor system has been recently suggested, by simultaneously assessing morphometric and susceptibility changes of striatonigral pathway and their possible correlations with clinical variables. Methods: In this cross-sectional study, we investigated possible differences in terms of Quantitative Susceptibility Mapping (QSM) values and volumes of different extrapyramidal relays, including striatum and substantia nigra (SN), in 30 FD patients (M/F = 11/19, mean age 42.6 +/- 12.2) and 37 healthy controls (HC) (M/F = 16/21, mean age 43.2 +/- 14.6). Patients underwent a clinical examination for the study of different motor functions, and the relationship between MRI and clinical variables was tested using the Spearman's coefficient. Results: Compared to HC, FD patients showed an increase in susceptibility values of the SN (p < 0.001) and striatum (p = 0.001), while no difference emerged for the other tested extrapyramidal structures, suggesting their relative sparing. The increased susceptibility was coupled to a reduced volume of the SN (p < 0.001), but not of the striatum (p = 0.34). Finally, no significant correlation emerged when probing the relationship between these modifications and the clinical variables. Conclusion: In FD patients, susceptibility and volumetric alterations are present throughout the extrapyramidal pathway, with the SN being particularly affected by these changes. Such results are in line with the subtle extrapyramidal involvement recently suggested in FD, and could further contribute to the understanding of the physiopathological bases of cerebral involvement in FD.

Background and Methods Mutations in WDR45 cause β-propeller protein-associated neurodegeneration (BPAN), a type of neurodegeneration with brain iron accumulation (NBIA). We reviewed clinical and MRI findings in 4 patients with de novo WDR45 mutations. Results Psychomotor delay and movement disorders were present in all cases; early-onset epileptic encephalopathy was present in 3. In all cases, first MRI showed: prominent bilateral SN enlargement, bilateral dentate nuclei T2-hyperintensity, and corpus callosum thinning. Iron deposition in the SN and globus pallidus (GP) only became evident later. Diffuse cerebral atrophy was present in 3 cases. Conclusions In this series, SN swelling and dentate nucleus T2 hyperintensity were early signs of BPAN, later followed by progressive iron deposition in the SN and GP. When clinical suspicion is raised, MRI is crucial for identifying early features suggesting this type of NBIA.

Fabry disease (FD) is a rare X-linked disorder characterised by abnormal progressive lysosomal deposition of globotriaosylceramide in a large variety of cell types. The central nervous system (CNS) is often involved in FD, with a wide spectrum of manifestations ranging from mild symptoms to more severe courses related to acute cerebrovascular events. In this review we present the current knowledge on brain imaging for this condition, with a comprehensive and critical description of its most common neuroradiological imaging findings. Moreover, we report results from studies that investigated brain physiopathology underlying this disorder by using advanced imaging techniques, suggesting possible future directions to further explore CNS involvement in FD patients. • Conventional neuroradiological findings in FD are aspecific. • White matter hyperintensities represent the more consistent brain imaging feature of FD • Abnormalities of the vasculature wall of posterior circulation are also consistent features. • The pulvinar sign is not reliable as a finding pathognomonic for FD. • Advanced imaging techniques have increased our knowledge about brain involvement in FD.

Background Vertebral Haemangiomas (VHs) are frequent and generally asymptomatic benign tumors, involving the spine, usually incidentally found on computed tomography and magnetic resonance. Despite being usually asymptomatic and quiescent lesions, VHs can occasionally manifest aggressive features, leading to clinical manifestations such as back pain and neurological deficits. Case report. We report a case of a 54-year-old man, presented with 5 months history of pain, associated with lower limbs paraesthesia and weakness, gait disturbance and episodes of accidental falls. Radiological evaluation by spine pre- and post-contrast MRI indicated multiple vertebral hypervascular lesions, compatible with haemangiomas, involving from T3 to T11 levels, showing several different features (typical and atypical); aggressive haemangioma radiological pattern may be valuable at T3 and T4 vertebras. A thoracic spine pre- and post-contrast computed tomography confirmed the radiological diagnosis of multiple aggressive haemangiomas. Discussion Aggressive VH consists in a very rare subset of vertebral haemangiomas characterized by a greater tendency in being symptomatic. They may show atypical radiological features, that make their diagnosis very complex. In the recent years, many strategies for treatment of symptomatic or aggressive VHs have been developed, but the optimal treatment strategy is still controversial. Conclusion Although aggressive VHs being extremely rare, recognizing radiological features of these lesions is mandatory to achieve a correct diagnosis and appropriate therapeutic targets.

Purpose: The aim of the study is to compare the accuracy of unstructured preoperative Computed Tomography (CT) reports from non-tertiary diagnostic centers with intraoperative findings in a large cohort of patients with Chronic Otitis Media (COM) undergone surgery.Methods: From 2012 to 2019, a total number of 301 patients were considered for our purposes. All patients with clinical evidence of COM had preoperative non-contrast high resolution CT scan of the temporal bone in non-tertiary diagnostic centers, performed within 3 months before surgery.Results: The accuracy of CT reports was analyzed in terms of nature, anatomical site, disease extension, bony erosion, vascular structures abnormalities relevant to surgical planning, and Eustachian tube patency. Compared to post-surgical findings, CT reporting critical analysis revealed a tendency to overestimation of bony erosion, coupled to underestimated description of facial canal/lateral semi-circular canal, vascular structures, and Eustachian tube.Conclusion: Discrepancies between CT reports and surgical findings in middle ear opacification can be at least in part due to limited expertise of general radiologists in ENT neuroimaging. To limit this lack of information and the limited accuracy of middle ear structures depiction, here we propose a structured checklist to adopt in the case of a temporal bone CT scan for COM, in order to optimize the communication with surgeons and provide all the crucial information for an accurate surgical planning.

AIMS: The aim of this study is to assess the value of ultrasound in the differential diagnosis of orbital lesions. METHODS: One hundred and thirty-eight patients with clinical features of an orbital mass were examined by orbital ultrasound prior to undergoing surgery, from January 2000 to January 2017. All patients underwent excisional or incisional orbital biopsy. The results of orbital ultrasonography were compared with the final histological diagnosis. RESULTS: Orbital lesions were localized by ultrasonography in 133/138 cases (96.4%); the false-negative rate of orbital echography was 3.6% (5/138). The nature of the orbital lesions was correctly determined by ultrasonography in 54.3% of the cases (75/138) preoperatively (true positives). In 58/138 (42%) patients, there was no correspondence between the ultrasound diagnosis and the histological diagnosis (false positives). The sensitivity of orbital ultrasonography for the detection of an orbital mass was 93.75% (CI 87.87–99.63%), while the specificity yielded no meaningful result (CI 0.00–60.24%). Moreover, the specificity of orbital ultrasonography to identify a malignant tumor falls within a CI of 0–62.72%. CONCLUSIONS: Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive in displaying an orbital mass; however, the specificity in the differential diagnosis of orbital lesions is not meaningful, particularly if malignancy is suspected. The assessment of orbital diseases requires multiple diagnostic approaches to balance the strengths and weaknesses of each method.

Background/objectives Several studies supported the beneficial effects of the Mediterranean diet (MeDi) on chronic diseases. In Multiple Sclerosis (MS), the MeDi might interfere with systemic inflammatory state, gut microbiota, and comorbidities. The Med Diet Score (MDS) estimates the adherence to the MeDi and the cardiovascular (CV) risk. Aims of our study were i) to photograph lifestyle and diet habits of a southern Italy cohort of people with MS (pwMS), and ii) to investigate the impact of the MeDi on MS clinical outcomes. Subjects/methods We conducted a multi-center, cross-sectional study, enrolling 435 consecutive consenting pwMS, attending the outpatient clinics for routine follow-up visits. Participants underwent a clinical examination and a 29-item self-administered questionnaire on life and dietary habits. Disease phenotype, Expanded Disability Status Scale (EDSS), MS Severity Score (MSSS), waist circumference (WC), Body Mass Index (BMI), therapies, and comorbidities, were updated. MDS was assessed and correlated with current and retrospective clinical data. Results 75.8% of respondents were interested in nutrition, 72.8% were non-smokers, 52.9% performed physical activity, and 45.6% used food supplements. MDS was higher in pwMS with normal WC (p = 0.031), and inversely correlated with MSSS (p = 0.013) and EDSS (p = 0.012) at survey time. MDS did not correlate with the total number of relapses (before and after diagnosis) (p = 0.372). Metabolic comorbidities were associated with an increased 10-year CV risk (r = 0.85, p = 0.002). Conclusion Our findings suggest a putative beneficial effect of the MeDi on WC, MS course and disability. Given the role of chronic systemic inflammation in maintenance of autoimmunity and secondary neurodegeneration, both involved in long-term disability, we may suppose a beneficial effect of the MeDi on MS long-term disability outcomes, probably mediated by a modulation of the gut microbiota and the low-grade chronic systemic inflammation.

In this study, we evaluated the possible relationship between the changes in retinal vessel density (VD) by optical coherence tomography angiography (OCTA) and the vascular alterations involving renal, cardiovascular and central nervous systems in patients affected by Fabry disease (FD). In 50 FD patients, the retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) in macular region were evaluated by OCTA examination. The patients also underwent a brain magnetic resonance imaging scan, renal and echocardiographic examinations with quantification of systolic pulmonary arterial pressure (PAPs) and left atrial volume index (LAVi). The VD of SCP and DCP was inversely related with E/e&rsquo, ratio, LAVi, interventricular septal thickness, global longitudinal strain (GLS) and PAPs (p &lt, 0.05). No relationship was found, with a multivariate analysis, between OCTA parameters and kidney function and neuroradiological signs of central nervous system involvement. OCTA could be a new vascular biomarker in FD, revealing a strong correlation between retinal capillary damage and myocardial impairment, possibly preceding both renal dysfunction and cerebrovascular involvement.

Introduction In recent years, cerebellar abnormalities have gained increasing attention as possible physiopathological substratum of idiopathic cervical dystonia (ICD), but a consistent pattern of cerebellar structural modifications has not yet been established. We systematically investigated the presence of volumetric alterations of cerebellar gray (GM) and white matter (WM) in ICD patients, as well as their clinical relevance. Methods In this two-centers prospective cross-sectional study, from May 2013 to December 2017, 27 patients with ICD and 27 age- and sex-comparable healthy controls underwent brain MRI including 3D T1-weighted sequences for volumetric analyses. Between-group differences in terms of gray matter and cerebellar peduncles volumes were investigated using both region of interest (ROI)-based and voxel-based approaches using the SUIT tool (SPM12), and significant volumetric changes were correlated with clinical impairment (as measured with the Tsui score) and presence of tremor. Results ICD patients showed significant volumetric reduction of cerebellar GM in the anterior lobe and lobule VI, resulting from both ROI-based (p ≤ 0.009) and voxel-based (p ≤ 0.04) analyses, while small clusters of reduced WM volume were found in the right cerebellum and left midbrain (p = 0.04), along with reduced volume of the bilateral superior (p = 0.04) and middle (p = 0.03) cerebellar peduncles. Furthermore, higher middle cerebellar peduncles volume was associated with the presence of tremor (p = 0.04). Conclusion Our data show evidence of a specific pattern of cerebellar structural abnormalities in ICD patients, with volume loss mainly involving cortical GM regions related to the somatotopic representation of the affected body parts and, to a lesser extent, cerebellar peduncles.

Background: Multi-parametric MRI used for preoperative assessment of orbital lesions does not routinely include DCE-MRI, since its accuracy in differential diagnosis of orbital mass is still under debate. Aim of this study is to characterize orbital lesions by multi-parametric MRI, analysing the incremental predictive value of DCE-MRI in differential diagnosis of orbital lesions. Methods: In this prospective triple-blind study, 43 consecutive patients with unilateral orbital lesion underwent conventional multimodal MRI and DCE-MRI before biopsy in a tertiary referral centre. Pre-operative MRI examination including conventional unenhanced MRI protocol, DWI with ADC maps, static CE 3D-T1 w and dynamic CE T1 w sequences, was performed within 1 week from surgery (anterior/lateral orbitotomy depending on location of the lesion, to carry out incisional/excisional biopsy). Results: Comparison between conventional T1 w/T2 w, DWI, CE 3D-T1 w and DCE-MRI groups showed a statistically significant difference in scores distribution (p

Ocular adnexal aterio-venous malformations (AVMs) are rare congenital disabling anomalies, which may enlarge causing disfiguring deformity and rarely severe hemorrhage. These lesions are generally treated by preliminary endovascular embolization to shrink the arterio-venous malformation, followed by surgical gross total resection. The authors report a case of eyelid arterio-venous malformation in a 12-year-old girl, which progressively increased in size in few months. The patient complained mild itching, blurring of the vision, and mild tenderness. Magnetic resonance imaging showed an expansive mass with multiple arterial vessels at the left superior eyelid and left forehead. The diagnosis of arterio-venous malformation was then confirmed by digital subtraction angiography. Primary surgical excision was excluded because of the high risk of intrasurgical bleeding. Embolization through superselective cannulation of the left external carotid feeder vessels was performed resulting in flow exclusion up to the 80% of the nidus. Subsequent surgical resection was not recommended due to clinical evidence of keloid-prone skin.

Background No information is currently available regarding the natural history of asymptomatic intracranial aneurysms in beta-thalassemia, raising several concerns about their proper management. Methods We performed a prospective longitudinal three-year-long MR-angiography study on nine beta-thalassemia patients (mean-age 40.3 ± 7.5, six females, 8 transfusion dependent) harboring ten asymptomatic intracranial aneurysms. In addition, we analyzed the clinical files of all adult beta-thalassemia patients (160 patients including those followed with MR-angiography, 121 transfusion dependent) referring to our Centers between 2014 and 2019 searching for history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. Results At the end of the three-year-long follow-up, no patient showed any change in the size and shape of the aneurysms, none presented new intracranial aneurysms or artery stenoses, none showed new brain vascular-like parenchymal lesions or enlargement of the preexisting ones. Besides, in our database of all adult beta-thalassemia patients, no one had history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. Conclusions Incidental asymptomatic intracranial aneurysms do not seem to be associated, in beta-thalassemia, with an increased risk of complications (enlargement or rupture) at least in the short term period, helping to optimize human and economic resources and patient compliance during their complex long-lasting management.

Aim of this study was to investigate the reliability and validity of 2D linear measures of ventricular enlargement as indirect markers of brain atrophy and possible predictors of clinical disability. In this retrospective longitudinal analysis of relapsing-remitting MS patients, brain volumes were computed at baseline and after 2 years. Frontal horn width (FHW), intercaudate distance (ICD), third ventricle width (TVW), and 4th ventricle width were obtained. Two-dimensional measures associated with brain volume at correlation analyses were entered in linear and logistic regression models testing the relationship with baseline clinical disability and 10-year confirmed disability progression (CDP), respectively. Possible cutoff values for clinically relevant atrophy were estimated via receiver operating characteristic (ROC) analyses and probed as 10-year CDP predictors using hierarchical logistic regression. Eighty-seven patients were available (61/26 = F/M; 34.1 ± 8.5 years). Moderate negative correlations emerged between ICD and TVW and normalized brain volume (NBV; p

Background : Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients’ immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment. Methods : A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start. Results : During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later. Discussion and conclusions : Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins.

Skull base osteomyelitis (SBO) is an invasive infection refractory to therapy, closely linked with malignant otitis externa (MOE). It is characterized by a mild clinical presentation that can delay cross-sectional imaging considered as the key to revealing it. Skull base osteomyelitis typically affects elderly diabetics and immunocompromised patients (>70 years). It most commonly has an otogenic origin due to an extension of MOE. The prognosis can be very poor without the administration of adequate and timely therapy at an early disease stage. Nowadays, Pseudomonas aeruginosa remains the most common pathogen associated with SBO. Fungi are a rare cause of MOE. This report documents a rare case of otogenic SBO caused by Candida parapsilosis in a diabetic patient, with persistent otologic symptoms as clinical onset and resistance to medical treatment. Fungal MOE has more subtle symptoms and is more aggressive than its bacterial counterpart. When MOE is resistant to antibacterial drugs, this should raise the suspicion of a fungal etiology of MOE. The current guidelines do not exhaustively describe the diagnosis, antifungal drugs of choice, and optimum duration of treatment. The description of these rare clinical cases should help with the multidisciplinary management of this disease in order to optimize the diagnosis and therapeutic protocol.

The paper pursues an investigation on an apocryphal text still underinvestigated by scholars: the Urbano, falsely attributed to Boccaccio. The first part focuses on its fortune in the Boccaccio’s canon, from the first edition of the Vocabolario della Crusca to the Boccaccio’s complete works edited in the Ottocento; furthermore, are pointed out its connections with the Libellus de Constantino Magno eiusque matre Helena, the main source of the plot, and with other genealogical medieval tales, such as the Libro imperiale and the Manfredo. The second part focuses on the manuscript tradition of the text, in order to demonstrate as its circulation in Quattrocento’s miscellaneous manuscripts of rhetorical texts in the vernacular, containing several texts by Boccaccio, has probably influenced the spurious attribution.

Background: Recent studies have suggested the presence of a significant atrophy affecting the cerebellar cortex in Friedreich ataxia (FRDA) patients, an area of the brain long considered to be relatively spared by neurodegenerative phenomena. Cognitive deficits, which occur in FRDA patients, have been associated with cerebellar volume loss in other conditions. The aim of this study was to investigate the correlation between cerebellar volume and cognition in FRDA. Methods: Nineteen FRDA patients and 20 healthy controls (HC) were included in this study and evaluated via a neuropsychological examination. Cerebellar global and lobular volumes were computed using the Spatially Unbiased Infratentorial Toolbox (SUIT). Furthermore, a cerebellar voxel-based morphometry (VBM) analysis was also carried out. Correlations between MRI metrics and clinical data were tested via partial correlation analysis. Results: FRDA patients showed a significant reduction of the total cerebellar volume (p = 0.004), significantly affecting the Lobule IX (p = 0.001). At the VBM analysis, we found a cluster of significant reduced GM density encompassing the entire lobule IX (p = 0.003). When correlations were probed, we found a direct correlation between Lobule IX volume and impaired visuo-spatial functions (r = 0.58, p = 0.02), with a similar correlation that was found between the same altered function and results obtained at the VBM (r = 0.52; p = 0.03). Conclusions: With two different image analysis techniques, we confirmed the presence of cerebellar volume loss in FRDA, mainly affecting the posterior lobe. In particular, Lobule IX atrophy correlated with worse visuo-spatial abilities, further expanding our knowledge about the physiopathology of cognitive impairment in FRDA.

Purpose Fabry Disease (FD) has been frequently proposed as possible underestimated differential diagnosis of Multiple Sclerosis (MS), but no study has been performed to test prevalence of GLA gene mutations in a population fulfilling diagnostic criteria of MS. Aim of this study is to determine the prevalence of GLA gene mutations in a large and representative population diagnosed with MS, simultaneously providing a critical revision of current literature reports of coexistence or misdiagnosis between these two conditions. Methods In this mono-centric cross-sectional study, 927 patients fulfilling McDonald diagnostic criteria and encompassing all MS phenotypes were enrolled. Patients underwent evaluation of α-GalA activity and genotyping. Both genetic variants annotated as pathogenic and GVUS were considered. Estimated alleles frequencies were then compared to the ones reported in the gnomAD database. Results GLA gene variants were found in seven individuals. Five patients carried variants previously described having controversial impact on FD phenotype, and the analysis of exome database revealed that they are not rare among healthy individuals. One patient showed a new variant never described before, and another one carried a late-onset FD cardiac variant. Conclusions The overall prevalence of GLA gene variants in MS patients is comparable to the one estimated in healthy population. This result is further supported by critical revision of current literature evidences of misdiagnosis between MS and FD, arguing in favour of independence between these disorders.

Osteoid osteomas are benign but painful bone-forming tumors usually involving long bones, with localization at the spine in 10-20% of the cases. The most common symptom is back pain responding to nonsteroidal anti-inflammatory drugs, but in some cases, also radicular pain can be present. For years, surgical excision has been considered the best choice of treatment for cases with unresponsive pain and has been practiced with a high percentage of success but also a high rate of fusion with instrumentation. In the last years, percutaneous radiofrequency ablation has been proposed as a new mini-invasive technique for the treatment of osteoid osteomas.

Case series Patients: Male, 74-year-old • Male, 76-year-old • Male, 77-year-old Final Diagnosis: Malignant otitis externa Symptoms: Edema • facial paralysis • hearing loss • otalgia and major otorrhea in the right ear Medication: — Clinical Procedure: ENT examination Specialty: Otolaryngology Objective: Unusual clinical course Background: Malignant external otitis (MEO) is an invasive infection that can involve the external auditory canal and the skull base up to the contiguous soft tissues. Considering the changing face of MEO, we reviewed cases of MEO treated in our Ear Nose Throat (ENT) clinic – University Federico II of Naples between 2018 and 2019 to evaluate the current epidemiology of the condition and to assess the state of art on diagnosis, therapeutic and follow-up management in our patients. Case Reports: We present the cases of three male patients with Type 2 diabetes mellitus who complained of long-lasting otorrhea and pain, with clinical suspicion of MEO. In all cases, ear swab was positive for Pseudomonas aeruginosa. All our patients received a 6-week course of intravenous ciprofloxacin, piperacillin, and tazobactam, with rapid clinical symptoms improvement and complete recovery at 1-year follow-up. Conclusions: MEO is difficult to treat due to the lack of standardized care guidelines. Patients with MEO often present with severe otalgia, edema, otorrhea, and facial nerve paralysis. Clinicians must suspect MEO in elderly diabetic and immunocompromised patients with persistent otalgia after external otitis. Imaging (computed tomography and magnetic resonance imaging) can play synergistic roles in the management of MEO. To evaluate eradication of the disease, clinicians have to assess clinical symptoms and signs as well as radiological imaging and inflammatory markers.

The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18–66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p

Background: Patient-reported outcomes (PROs) may help patients and clinicians in selecting disease-modifying therapies (DMTs) for multiple sclerosis (MS). Objective: To evaluate PRO differences among first-line DMTs for relapsing-remitting (RR) people with MS (pwMS). Methods: Multicenter study. RR pwMS on first-line DMTs completed Fatigue Severity Scale (FSS), PROs Indices for MS (PRIMUS), 36-item Short-Form Health Survey (SF-36), treatment satisfaction questionnaire for medication (TSQM), Beck Depression Inventory-II (BDI-II), and Symbol Digit Modalities Test (SDMT). Differences among PROs across DMTs were tested by ANOVA. Multivariable linear regressions were used to investigate associations between PROs and the treatment group. Results: Two-hundred eighty pwMS were enrolled: 56% were on interferons (INF), 22% on dimethylfumarate (DMF), 13% on glatiramer acetate, and 9% on teriflunomide (Teri). Compared with INF, pwMS on Teri were the oldest, with higher disability, worst depression at BDI, worst cognitive performances at SDMT (p = 0.001), fatigue at FSS (p = 0.001), and activity limitation and quality of life respectively at PRIMUS (p = 0.005) and SF-36 Mental Composite Score (p < 0.001); pwMS on DMF reported highest side effects and, together with pwMS on Teri, better treatment satisfaction at TSQM. Conclusions: Compared with INF-treated patients, pwMS on DMF and Teri reported the best treatment satisfaction, although DMF-treated pwMS reported higher side effects and those on Teri the worst QoL and fatigue; however, the older age, higher disability and depression, and worse cognitive performance of pwMS on Teri suggest to be careful in evaluating these results.

Chondrosarcoma is a rare malignant tumour arising from the cartilage with a high variability in the clinicalcourse and overall prognosis. This entity has, generally, a predilection for long bones of the limbs and pelvis and the location in the cranial bones is quite rare. We report a case of a 38 year male with a large and poorly symptomatic parafalcine chondrosarcoma of the cranial vault which was removed en bloc. The described location is extremely rare. Magnetic Resonance Imaging permitted to better delineate the lesion and plan the most appropriate therapeutic approach. Final diagnosis was based on histological examination, which confirmed the hypothesis of low-grade parafalcine chondrosarcoma. Even though surgery remains the mainstay of treatment for cerebral chondrosarcomas, adjuvant radiotherapy such as stereotactic, proton beam or carbon ion-beam therapy might be necessary in aggressive or incomplete removed cases.

Background: Dimethyl-fumarate (DMF) was effective and safe in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. Methods: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. Results: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0–8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18–0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p =

Objectives A strikingly increased headache prevalence was recently noted in Sri Lankan beta-thalassemia patients, raising several concerns regarding long-term neurological involvement in this condition. Methods We interviewed on headache occurrence and characteristics 102 Italian beta-thalassemia patients and 129 healthy controls. 3T-MRI, MR-angiography, MR-venography, cognitive and psychiatric findings were considered. Results Headache was diagnosed in 39/102 (38.2%) beta-thalassemia patients without significant phenotype-related differences and in 51/129 (39.5%) controls. Patients and controls did not differ significantly regarding episode number (5.9 ± 6.2 vs 5.4 ± 4.4 days/month), subjective severity-score (6.8 ± 1.4 vs 7.1 ± 1.3), age-at-onset (24.3 ± 13.0 vs 19.5 ± 9.6 years) and headache-subtype rate. No main demographic, clinical or laboratory data was associated with headache but female gender. Headache was not associated with white matter lesions (number or maximal diameter), intracranial aneurysms, intracranial artery stenoses or venous sinus thrombosis. Cognitive and psychiatric evaluations were worse in beta-thalassemia, however, headache did not correlate with full-scale Intelligence Quotient (75.4 ± 18.0 vs 76.7 ± 15.3, with and without headache, respectively) or Brief Psychiatric Rating Scale scores (29.1 ± 2.7 vs 28.5 ± 3.4). Conclusions Among Italian beta-thalassemia patients, headache does not seem to be more common or severe than in the general population. In addition, patients with headache do not seem to present increased conventional MRI, MR-angiography and cognitive/psychiatric changes.

Purpose Inverted papilloma (IP) is a tumor usually arising from sinonasal cavities, with tendency for recurrence and possible malignant transformation. Along with endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) play a crucial role in defining preoperative staging, tumor origin, and possible differential diagnosis, with significant repercussions on therapeutic planning. However, at present no consensus has been reached concerning IP diagnostic workup. Aim of this study is to assess CT and MRI sensitivity and specificity in identifying IP imaging hallmarks, evaluating their global diagnostic accuracy in order to define a novel diagnostic flowchart. Methods We retrospectively analyzed multimodal imaging of patients with histologically confirmed IP and mimics. Two neuroradiologists in consensus retrospectively rated the presence of typical imaging features of IP, both on CT and MRI scans. Sensitivity, specificity and diagnostic accuracy were assessed for both the techniques. Final results were expressed as ROC curves and relative areas under the curve (AUC). Results The AUC considering CT parameters were 0.42, whereas the AUC considering MRI parameters were 0.54. Combining the 2 techniques and limiting the evaluation to the most distinctive features such as focal hyperostosis and CCP, the AUC was 0.79. Conclusion MRI can provide better tissue characterization and higher diagnostic accuracy in case of suspected IP, whereas CT is more useful in determining bony involvement. Here we propose a possible diagnostic flowchart for IP, based on the assumption that the combination of the imaging techniques allows to optimize the clinical assessment and the subsequent therapeutic planning.

Purpose: Beside the well-known accuracy of non-EPI DWI techniques and relative ADC maps in detecting cholesteatomatous tissue, ADC can also represent a useful tool for stratifying cholesteatoma risk of recurrence. Aim of this study is to test the role of ADC in determining risk of recurrence for primary middle ear cholesteatoma, proposing stratification based on pre-operative mean (mADC) and normalized (nADC) ADC values. Methods: In this prospective study, 60 patients with primary unilateral middle ear cholesteatoma underwent a three-years-long follow-up to assess the presence of recurrent disease after macroscopically complete excisional surgery. Baseline MRI examination mADC and nADC values in the group with early evidence of recurrent cholesteatoma were compared to the group with no evidence of recurrence by using T statistics. Results: ADC values on pre-operative MRI examination were lower in cholesteatomas with early evidence of recurrence, and statistical significance was slightly higher for nADC compared to mADC measurements. We also determined a cut-off between the two groups, proposing stratification in high-risk of recurrence cholesteatomas (mADC≤ 1000 or nADC< 1.3) and low-risk cholesteatomas (mADC>1000 or nADC≥1.3). Conclusions: ADC values resulted discriminating in identifying cholesteatomas with higher risk of early recurrence, both for mean and normalized ADC, with optimized tissue characterization and outcome prediction.

Objective: The aim of this study was to perform the first resting-state func- tional MRI (RS-fMRI) analysis in Friedreich’s ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances. Methods: In total, 24 FRDA patients (M/F: 15/9, mean age 31.3 15.0) and 24 healthy controls (HC; M/F: 15/9, mean age 30.7 15.5) were enrolled in this cross-sectional study. All patients underwent a thorough neuropsychological battery, investigat- ing different cognitive domains. RS-fMRI data were analyzed using a seed-based approach, probing the FC of cortical areas potentially referable to specific exec- utive and cognitive functions compromised in FRDA. Results: Compared to HC, FRDA patients showed overall worse neuropsychological scores in several domains, including global cognitive assessment, spatial memory, visuopercep- tion and visuospatial functions, and executive functions. Analysis of RS-fMRI data showed a higher FC in FRDA patients compared to HC between paracin- gulate gyri and the medial frontal gryrus, between the superior frontal gyrus and bilateral angular gyri, and between the middle temporal gyrus and the cin- gulate gyrus, with a reduced FC between the medial frontal gryrus and the cere- bellum. Interpretation: We found a reduction in FC between frontal areas and the contralateral cerebellar cortex in FRDA, in line with the known alteration in cerebello-cortical pathway in this condition. On the other hand, a higher FC between different cortical areas was shown, possibly reflecting a compensatory phenomenon. These results, in conjunction with clinical findings, may shed new light on the pattern of supratentorial and infratentorial involvement, and on dynamics of brain plasticity in this disease.

Background: Fabry disease (FD) is a X-linked recessive lysosomal storage disorder characterized by altered biodegradation of glycosphingolipids. It is a multisystem pathology, also involving ophthalmological systems that show modifications of the vessel wall due to glycosphingolipid deposits. Optical coherence tomography angiography (OCT-A) allows for an objective analysis of retinal microvasculature alterations, evaluating retinal vessel density in macular region. Methods: A total of 54 FD patients (34 females, 20 males, mean age 44.1 &plusmn, 15.6 years) and 70 controls (36 females, 34 males, mean age 42.3 &plusmn, 15.6 years) were included in this study. We evaluated vessel density in different macular areas (whole image, fovea, and parafovea) of both the superficial capillary plexus (SCP) and of the deep capillary plexus (DCP). Results: In the SCP there was a significantly lower vascular density in patients compared with controls in whole image (49.95 &plusmn, 5.17% vs. 51.99 &plusmn, 2.52%, p &lt, 0.001), parafovea (52.01 &plusmn, 6.69% vs. 54.30 &plusmn, 2.61%, p = 0.002), and fovea (22.38 &plusmn, 9.01% vs. 29.31 &plusmn, 5.84%, 0.0001). In the DCP the vessel density was statistically increased in each macular area in patients compared with controls (54.82 &plusmn, 8.07% vs. 50.93 &plusmn, 5.46%, p = 0.005, 57.76 &plusmn, 7.26% vs. 53.59 &plusmn, p = 0.0001, and 39.75 &plusmn, 8.59% vs. 34.43 &plusmn, 8.68%, 0.0001 for whole image, parafovea, and fovea, respectively). Conclusion: OCT-A analysis showed that the macular vessel density was significantly reduced in the SCP and increased in the DCP in FD patients compared with controls. These findings, which might be a consequence of the alteration of vascular wall occurring in FD, support the hypothesis that the evaluation of early retinal microvascular network changes could be a useful tool in the clinical evaluation of the disease.

Highlights • Iron overload is a life-threatening condition in beta-thalassemia. • Data on brain involvement in systemic iron overload are conflicting. • MRI quantification of brain tissue iron content is feasible in a voxel-based approach. • No iron tissue excess is evident in beta-thalassemia but in the choroid plexuses., Objective Multisystem iron poisoning is a major concern for long-term beta-thalassemia management. Quantitative MRI-based techniques routinely show iron overload in heart, liver, endocrine glands and kidneys. However, data on the brain are conflicting and monitoring of brain iron content is still matter of debate. Methods This 3T-MRI study applied a well validated high-resolution whole-brain quantitative MRI assessment of iron content on 47 transfusion-dependent (mean-age: 36.9 ± 10.3 years, 63% females), 23 non-transfusion dependent (mean-age: 29.2 ± 11.7 years, 56% females) and 57 healthy controls (mean-age: 33.9 ± 10.8 years, 65% females). Clinical data, Wechsler Adult Intelligence Scale scores and treatment regimens were recorded. Beside whole-brain R2* analyses, regional R2*-values were extracted in putamen, globus pallidum, caudate nucleus, thalamus and red nucleus; hippocampal volumes were also determined. Results Regional analyses yielded no significant differences between patients and controls, except in those treated with deferiprone that showed lower R2*-values (p

Different studies showed correlations between gadolinium-based contrast agent (GBCA) administrations and dentate nucleus (DN) T1-weighted hyperintensity. The clinical impact of gadolinium retention, however, is still largely unknown. The aim of this study was to investigate relations between MRI and clinical disability in relapsing–remitting multiple sclerosis (RR-MS) patients. In this retrospective study, clinical data were obtained from 74 RR-MS patients at baseline and after a mean follow-up time of 3.6 years, including the expanded disability status scale (EDSS) score and its change (ΔEDSS). Patients were considered showing clinical worsening if they score a ΔEDSS ≥ 1 (for baseline EDSS ≤ 5.5) or ΔEDSS ≥ 0.5 (for baseline EDSS > 5.5). From the MRI data, the presence of bilateral DN hyperintensity was recorded along with the calculation of longitudinal relaxation rate (R1) maps. Patients with DN hyperintensity showed similar ΔEDSS change compared to those without visible changes on T1-weighted images (p = 0.32). Similarly, no DN-R1 difference was found comparing stable patients with those showing a significant clinical worsening (p = 0.54). Finally, no significant effect of DN-R1 values explained the variance in ΔEDSS (p = 0.76), thus suggesting their independence from the clinical outcome. MS patients with DN hyperintensity show similar EDSS changes compared to subjects without DN high-signal intensity. Furthermore, mean DN-R1 values of patients with significant clinical worsening were comparable to those of stable subjects and were unrelated to clinical disability. Taken together, these findings suggest that gadolinium retention in the brain of MS patients does not affect their clinical worsening, expressed by the EDSS change.

Highlights • CLIPPERS is a recently described, underestimated CNS inflammatory disorder involving midbrain and cerebellum. • Unusual clinical presentation can make the diagnosis particularly challenging to the clinician. • MRI plays a pivotal role in the correct diagnostic assessment, helping discriminate CLIPPERS from potential mimickers., Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids syndrome (CLIPPERS) is a newly described, underestimated CNS inflammatory disorder involving predominantly the midbrain and the cerebellum. CLIPPERS pathogenesis is largely unknown, and its clinical manifestations are polymorphic and sometimes confounding. Recently clinical, radiological and pathological diagnostic criteria have been proposed to discriminate CLIPPERS from potential mimickers, but the diagnosis still remains challenging. Here we present the case of a patient with radiological findings consistent with CLIPPERS but with atypical clinical presentation, highlighting the importance of a proper diagnostic assessment.

Multi-factorial causes jeopardize brain integrity in β-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young β-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic β-thalassaemia patients (mean-age 35·2±10·7years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9±10·8years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0±10·6 vs. 4·6±9·1, P=0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic β-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.

Cognitive involvement in beta-thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically-asymptomatic beta-thalassaemia patients (mean-age 34 center dot 5 +/- 10 center dot 3 years; 53 transfusion-dependent [TDT], 21 non-transfusion dependent [NTDT]) and 45 healthy volunteers (mean-age 33 center dot 9 +/- 10 center dot 7 years). Participants underwent testing with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T-magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full-Scale Intelligence Quotient (FSIQ) than controls (75 center dot 5 +/- 17 center dot 9 vs. 97 center dot 4 +/- 18 center dot 1, P < 0 center dot 0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P = 0 center dot 08) but a similar cognitive profile at WAIS-subtests. FSIQ correlated with total and indirect bilirubin (P P = 0 center dot 002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance-angiography findings, brain tissue iron content or other disease-related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28 center dot 74 +/- 3 center dot 1 vs. 27 center dot 29 +/- 4 center dot 8, P = 0 center dot 01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84 center dot 4% vs. 64 center dot 9%, P = 0 center dot 004) and correlated with higher FSIQ (P = 0 center dot 001) and education level (P = 0 center dot 001). In conclusion, Italian adult beta-thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long-term socio-economic consequences.

Background Multiple Sclerosis (MS) is considered among possible differential diagnosis of Fabry Disease (FD), especially in early stages when findings are suggestive but not diagnostic for MS. We report the case of a family in which FD and MS coexist, offering an overview on clues for differential diagnosis and speculating on shared etiopathogenic mechanisms for these conditions. Methods Taking as starting point the diagnosis of FD in a dialysis patient during a screening programme, we retrospectively rebuilt his family history and revised clinical and imaging examinations of his five siblings, two of which with previous diagnosis of MS. Results After genetic testing, two subjects were found positive to a new α-galactosidase A mutation, probably causative for FD classical variant. The two subjects meeting diagnostic criteria for MS were found negative to any GLA gene mutation, therefore initial diagnosis was confirmed. The remaining two siblings resulted unaffected, with neither clinical nor instrumental evidence of FD and MS. Conclusions Differential diagnosis between FD and MS may be challenging, especially in early clinical stages when only extensive clinical evaluation and correct MRI interpretation may reduce the risk of misdiagnosis. Moreover this report allows speculating on potential etiological and pathogenic mechanisms, common both to FD and MS.

Purpose Myeloid sarcoma (MS) of the orbit is an uncommon condition in occurring in children, generally coupled to myeloproliferative neoplasms. Observations We describe two rare cases of orbital MS in young boys with aggressive local symptoms but without evidence of acute myeloid leukemia (AML), both patients underwent orbitotomy for gross-tumor resection and biopsy. At follow up, there was no evidence of recurrence nor evolution of the myeloproliferative neoplasms clinically and by radiological and laboratory work-up. We also provide a detailed description of the magnetic resonance imaging presentation, with an extensive pathological analysis correlation. Conclusions and importance A comprehensive revision of the literature on isolated orbital MS was carried out with particular emphasis on clues for differential diagnosis and treatment options, stressing the need to consider MS even in the absence of sign and symptoms of an underlying myeloproliferative disorders.

Background: Anderson-Fabry disease (AFD) can induce both central nervous system white matter lesions (WMLs) and cardiac abnormalities including left atrial (LA) dysfunction. We sought to evaluate the possible interrelations of LA structure and function impairment with the presence of WMLs in AFD patients. Methods 22 AFD patients and 22 controls, matched for age and sex, underwent an echo-Doppler exam including quantification of peak atrial longitudinal strain (PALS). AFD patients underwent also a 3-T brain magnetic resonance imaging with a visual quantification of WMLs by Fazekas&rsquo, score (FS) on 3D FLAIR images. Results AFD patients had significantly higher left ventricular (LV) mass index (LVMi) and relative wall thickness, and lower PALS compared to controls. Among AFD patients, 9 showed a FS = 0, and 13 a FS &gt, 1. AFD patients with FS &ge, 1 showed lower PALS (29.4 &plusmn, 6.7 vs. 37.2 &plusmn, 3.9%, p = 0.003) than those with FS = 0, without difference in LA volume index and LVMi. In AFD patients, FS was inversely related to PALS (r = &minus, 0.49, p &lt, 0.0001), even after adjusting for LVMi (r = &minus, 0.43, p &lt, 0.05). Conclusions In the absence of significant alterations in LA size, AFD patients had lower PALS compared to controls. The inverse association between PALS and presence of WMLs indicates a possible parallel early involvement of heart and brain.

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10−5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.

To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. Purpose: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. Methods: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. Results: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10− 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10− 3 mm2/s) group (p < 2.2 × 10− 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10− 3 mm2/s. Conclusions: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.