Midterm follow-up after embolization of intracranial aneurysms proximal to the circle of Willis with the Silk Vista flow diverter: the I-MAMA registry.

PURPOSE: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista "Mama" (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms. METHODS: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients' clinical presentation, aneurysms' size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up. RESULTS: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6-12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C). CONCLUSIONS: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate.

Efficacy of retrograde revascularization in diabetic patients with chronic limb-threatening ischemia after a failed antegrade approach.

BACKGROUND: Chronic limb-threatening ischemia is the end stage of peripheral arterial disease. The revascularization of patients suffering from diabetes mellitus who present chronic total occlusions of below-the-knee vessels can be technically very difficult and sometimes impossible to achieve by performing only an antegrade approach. As regards retrograde recanalization, several studies have investigated the efficacy and safety of this technique in the femoropopliteal axis or in the infrageniculate arterial vessels in patients with advanced atherosclerotic disease. Currently in the literature there are still few studies analyzing the effectiveness of the retrograde approach in the treatment of occlusions of below-the-knee vessels in patients suffering from diabetes mellitus. OBJECTIVES: The purpose of the study was to retrospectively evaluate safety, technical success, and clinical outcome of retrograde transpedal/transtibial recanalization in patients suffering from diabetes mellitus. RESEARCH DESIGN: This is a retrospective observational monocentric study. SUBJECTS: We retrospectively analyzed data over a three-year period (August 2019-September 2022) of patients that underwent revascularization of one or more below-the-knee vessels for chronic limb-threatening ischemia and had a retrograde transpedal/transtibial approach after a failed antegrade transfemoral revascularization. We identified and included in the study 28 out of 352 patients. MEASURES: We evaluated clinical comorbidities, Rutherford-Becker classification, Texas classification, and the occluded vessels (only below-the-knee or multi-level occlusions); we then analyzed technical, procedural and clinical success, survival rate, and procedural complications. All patients included in the study underwent a 6 months follow-up. RESULTS: Patients belonged to Rutherford-Becker stage V (18) or VI (10), Texas wound classification IIC: 7 IID: 8 IIIC: 4 IIID: 9, all suffering from diabetes, and five were on dialysis. Treatment of a femoropopliteal lesion was performed during the same procedure in 6 of 28 patients (28.6%). Technical success was obtained in 25 out of 28 patients (89.3%), and procedural success was achieved in 23 of 28 patients (82.1%). No complications occurred at the pedal/tibial access. One minor complication at the femoral access was observed. The cure rate 6 months after the procedure was 57.1% (16/28 patients), and the 6-month survival rate was 96.4%. Three major amputations (10.7%) and four minor amputations (14.2%) were performed after revascularization procedures. Two patients were readmitted for vascular causes (7.1%). CONCLUSIONS: Retrograde approach for revascularization of below-the-knee vessels in diabetic patients is safe and effective with high procedural and clinical success rates in the absence of significant complications. It should be considered when revascularization cannot be achieved with an antegrade transfemoral approach.

Multishell diffusion MRI reveals whole-brain white matter changes in HIV.

Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have been previously used to explore white matter related to human immunodeficiency virus (HIV) infection. While DTI and DKI suffer from low specificity, the Combined Hindered and Restricted Model of Diffusion (CHARMED) provides additional microstructural specificity. We used these three models to evaluate microstructural differences between 35 HIV-positive patients without neurological impairment and 20 healthy controls who underwent diffusion-weighted imaging using three b-values. While significant group effects were found in all diffusion metrics, CHARMED and DKI analyses uncovered wider involvement (80% vs. 20%) of all white matter tracts in HIV infection compared with DTI. In restricted fraction (FR) analysis, we found significant differences in the left corticospinal tract, middle cerebellar peduncle, right inferior cerebellar peduncle, right corticospinal tract, splenium of the corpus callosum, left superior cerebellar peduncle, left superior cerebellar peduncle, pontine crossing tract, left posterior limb of the internal capsule, and left/right medial lemniscus. These are involved in language, motor, equilibrium, behavior, and proprioception, supporting the functional integration that is frequently impaired in HIV-positivity. Additionally, we employed a machine learning algorithm (XGBoost) to discriminate HIV-positive patients from healthy controls using DTI and CHARMED metrics on an ROIwise basis, and unique contributions to this discrimination were examined using Shapley Explanation values. The CHARMED and DKI estimates produced the best performance. Our results suggest that biophysical multishell imaging, combining additional sensitivity and built-in specificity, provides further information about the brain microstructural changes in multimodal areas involved in attentive, emotional and memory networks often impaired in HIV patients.

Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

BACKGROUND AND PURPOSE: Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. METHODS: A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. RESULTS: Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-ß-42/amyloid-ß-40 ratio. CONCLUSIONS: The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

Can machine learning of post-procedural cone-beam CT images in acute ischemic stroke improve the detection of 24-h hemorrhagic transformation? A preliminary study.

PURPOSE: Hemorrhagic transformation (HT) is an independent predictor of unfavorable outcome in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT). Its early identification could help tailor AIS management. We hypothesize that machine learning (ML) applied to cone-beam computed tomography (CB-CT), immediately after EVT, improves performance in 24-h HT prediction. METHODS: We prospectively enrolled AIS patients undergoing EVT, post-procedural CB-CT, and 24-h non-contrast CT (NCCT). Three raters independently analyzed imaging at four anatomic levels qualitatively and quantitatively selecting a region of interest (ROI) < 5 mm2. Each ROI was labeled as "hemorrhagic" or "non-hemorrhagic" depending on 24-h NCCT. For each level of CB-CT, Mean Hounsfield Unit (HU), minimum HU, maximum HU, and signal- and contrast-to-noise ratios were calculated, and the differential HU-ROI value was compared between both hemispheres. The number of anatomic levels affected was computed for lesion volume estimation. ML with the best validation performance for 24-h HT prediction was selected. RESULTS: One hundred seventy-two ROIs from affected hemispheres of 43 patients were extracted. Ninety-two ROIs were classified as unremarkable, whereas 5 as parenchymal contrast staining, 29 as ischemia, 7 as subarachnoid hemorrhages, and 39 as HT. The Bernoulli Naïve Bayes was the best ML classifier with a good performance for 24-h HT prediction (sensitivity = 1.00; specificity = 0.75; accuracy = 0.82), though precision was 0.60. CONCLUSION: ML demonstrates high-sensitivity but low-accuracy 24-h HT prediction in AIS. The automated CB-CT imaging evaluation resizes sensitivity, specificity, and accuracy rates of visual interpretation reported in the literature so far. A standardized quantitative interpretation of CB-CT may be warranted to overcome the inter-operator variability.

Bithalamic infarction in a tentorial dural artero-venous fistula and thalamic dementia: a case report and systematic review.

PURPOSE: To report a case of bilateral thalamic infarction (BTI) presenting as progressive thalamic dementia due to a midline tentorial dAVF (TdAVF) and to provide a systematic review of the literature. METHODS: We performed a systematic literature review of previously reported cases of bi-thalamic signal changes due to dAVF considering population characteristics, clinical presentation, imaging findings, treatments, and outcomes. RESULTS: We found 29 papers from 1985 until 2021 describing 35 cases of BTI dAVF-related. We analysed 36 cases comprehensive of our case report. The mean age was 58.7 years (range 38-79), 91.6% were males (n=33). Most cases presented with a subacute syndrome. In 86.1% (n=31) of cases a TdAVF was found; 58.3% (n=21) were type 2 Borden-Shucart fistulas, the remaining were mostly type 3. In 80.5% (n=29), a thrombosed sinus was identified. 33.3% of cases (n=12) had bi-thalamic haemorrhages. Endovascular treatment was performed in 83.3% of cases (n=30). A total of 75% (n=27) of cases had a good recovery. CONCLUSIONS: BTIs due to dAVFs may present with subacute symptoms overlapping with several differential diagnoses. Prompt identification at MRI, before venous drainage failure and bleeding, is crucial for a good prognosis.

MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer's Disease.

Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer's disease, and with the complex group of pathologies commonly referred to as "disconnection syndromes." This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer's disease, highlighting the emerging biomarkers shared by both diseases.

Cardiac Computed Tomography Evaluation of Association of Left Ventricle Disfunction and Epicardial Adipose Tissue Density in Patients with Low to Intermediate Cardiovascular Risk.

Background and objectives: Epicardial adipose tissue density (EAD) has been associated with coronary arteries calcium score, a higher load of coronary artery disease (CAD) and plaque vulnerability. This effect can be related to endocrine and paracrine effect of molecules produced by epicardial adipose tissue (EAT), that may influence myocardial contractility. Using coronary computed tomography angiography (CCT) the evaluation of EAD is possible in basal scans. The aim of the study is to investigate possible associations between EAD and cardiac function. Material and Methods: 93 consecutive patients undergoing CCT without and with contrast medium for known or suspected coronary CAD were evaluated. EAD was measured on basal scans, at the level of the coronary ostia, the lateral free wall of the left ventricle, at the level of the cardiac apex, and at the origin of the posterior interventricular artery. Cardiac function was evaluated in post-contrast CT scans in order to calculate ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV). Results: A statistically significant positive correlation between EAD and ejection fraction (r = 0.29, p-value < 0.01) was found. Additionally, a statistically significant negative correlation between EAD and ESV (r = -0.25, p-value < 0.01) was present. Conclusion: EAD could be considered a new risk factor associated with reduced cardiac function. The evaluation of this parameter with cardiac CT in patients with low to intermediate cardiovascular risk is possible.

Early intracranial haemorrhages in acute promyelocytic leukaemia: analysis of neuroradiological and clinico-biological parameters.

Acute promyelocytic leukaemia (APL) represents a modern success of precision medicine. However, fatalities occurring within the first 30 days of induction treatment, in particular intracranial haemorrhage (ICH), remain the main causes of death. We studied the clinico-biological characteristics of 13 patients with APL who experienced ICH. Compared to 85 patients without this complication, patients with ICH were older and more frequently had high-risk APL. Moreover, positivity for the 'swirl' sign at neuroradiological imaging and hydrocephalus were predictors of a fatal outcome, together with lower fibrinogen, prolonged international normalized ratio (INR) and higher lactate dehydrogenase levels.

Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss.

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting-state functional MRI (rs-fMRI), in conjunction with graph-theoretical analysis and a newly developed functional "disruption index," to study whole-brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph-theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs-fMRI to study potential changes in brain connectivity. From rs-fMRI data, global and local graph-theoretical measures, disruption index, and audiological examinations were estimated. Mann-Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain-wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph-theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.

Neuroimaging findings in leukoencephalopathy with calcifications and cysts: case report and review of the literature.

Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a neurological disorder characterized by the radiological triad of white matter abnormalities, intracranial calcifications and cystic lesions variable in size resulting from a diffuse cerebral microangiopathy. Typically, progressive focal neurological deficits and seizures are the first clinical manifestation, but the severity of symptoms can vary according to the size and location of the cystic lesions holding compressive effects on the surrounding brain tissue. The most common histopathological finding is diffuse microangiopathy, which might be associated to pathogenic mutations in SNORD118 gene causing Labrune syndrome. Similar neuroradiological appearances have been found in the Coats plus syndrome, a systemic disorder caused by a genetic diffuse microangiopathy that affects not only the brain but also the retina and multiple organs, with a more complex clinical picture that address the diagnosis; biallelic mutations in CTC1 gene, encoding the conserved telomere maintenance component 1 (CTC1), are responsible of this systemic disorder. The aim of this contribution is to review the existing literature focusing on the neuroimaging characteristics by reporting cases in which radiological findings were highly suggestive for LCC.

Qualitative and quantitative analysis of 3D T1 Silent imaging.

PURPOSE: To compare brain magnetic resonance imaging (MRI) using T1 3D Silent and fast T1 3D Gradient-Echo (GRE) BRAin VOlume (known as BRAVO) sequences. The primary aim is to assess the quantitative and qualitative analysis of Silent and BRAVO images by the measurement of the contrast (C), the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The second aim is to estimate the subjective sound levels and the specific absorption rate (SAR). METHODS: Twenty-two subjects had T1 3D Silent and T1 3D BRAVO sequences added to the standard MR examination. The qualitative analysis of the two sequences was performed by two radiologists independently. The quantitative analysis was performed by placing regions of interest on the cerebrospinal fluid, on the white and grey matter. The C, the CNR and the SNR were calculated for each sequence. After each T1-3D sequence, subjects gave a score rating to evaluate the acoustic noise. Finally, the SAR was evaluated by the digital imaging and communications in medicine (DICOM) tags. RESULTS: The image quality scores obtained by the two radiologists were higher for BRAVO compared to the Silent. However, qualitatively, the Silent images were similar to BRAVO for diagnostic use. Quantitatively, CNR for GM-CSF was comparable in the two sequences and SNR in CSF was higher in Silent than BRAVO. The acoustic noise of Silent sequence was statistically lower compared with BRAVO. The maximum SAR measured was 1.4 W/kg. CONCLUSIONS: 3D T1 Silent can be a valid alternative technique to conventional BRAVO to reduce the acoustic noise preserving the diagnostic accuracy. However, radiologists preferred the conventional sequence to Silent.

Physical Exercise and Alzheimer's Disease: Effects on Pathophysiological Molecular Pathways of the Disease.

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.

Radiological imaging in multiple myeloma: review of the state-of-the-art.

PURPOSE: Multiple myeloma is a type of blood cancer arising from the uncontrolled clonal proliferation of malignant plasma cells resulting in impaired hematopoiesis, hyper production of monoclonal protein, bone tissue destruction leading and renal system alterations up to kidney failure. The aim is to review the state-of-the-art of radiological imaging in multiple myeloma. METHODS: Radiological techniques as well as the advancements in imaging technology have been reviewed and summarized. The main radiological findings of different imaging techniques in patients suffering from multiple myeloma are also illustrated. RESULTS: Different radiological techniques provide structural and functional data. In the last years, conventional skeletal survey has gradually lost its utility and it has been replaced by whole body low-dose computed tomography which allows to identify also small lytic lesions, the medullary and the extramedullary involvement. Nowadays, magnetic resonance is the most sensitive imaging technique for detecting of skeletal as well as medullary involvement in patients with multiple myeloma. Thanks to the multiparametric evaluation (morphological, diffusion weighted and perfusion imaging sequences) and to the quantitative analysis, magnetic resonance imaging is proved to be useful in the early evaluation of response to therapy. Finally, positron emission tomography has greater sensibility compared to computed tomography as it provides quantitative data; however, the lower expression levels of the specific gene involved in the glycolysis pathway are associated with false-negative results with consequent underestimation of the disease. CONCLUSION: The only use of the advanced combined multimodal imaging allows a better evaluation, staging and early assessment of treatment response in patients with multiple myeloma.

Comparison between synthetic and conventional magnetic resonance imaging in patients with multiple sclerosis and controls.

OBJECTIVES: Synthetic magnetic resonance imaging (SyMRI) allows to obtain different weighted-images using the multiple-dynamic multiple-echo sequence lasting 6 min. The aim is to compare quantitatively and qualitatively synthetic- and conventional MRI in patients with multiple sclerosis (MS) and controls assessing the contrast (C), the signal to noise ratio (SNR), and the contrast to noise ratio (CNR). We evaluated the lesion count and lesion-to-white matter contrast ([Formula: see text] in the MS patients. METHODS AND METHODS: 51 patients underwent synthetic- and conventional MRI. Qualitative analysis was evaluated by assigning scores to all synthetic- and conventional MRI sequences by two neuroradiologists. Lesions were counted in MS patients both in the conventional- and synthetic T2-FLAIR. Regions of interest were placed in the cerebrospinal fluid, in the white- and grey matter. For the sequences were evaluated: C, CNR, and SNR. RESULTS: Synthetic T2-FLAIR images are qualitatively inferior. C and CNR were significantly higher in synthetic T1W and T2W images compared to conventional images, but not for T2-FLAIR. The SNR value was always lower in synthetic images than in conventional ones. CONCLUSIONS: SyMRI can be used in clinical practice because it has a similar diagnostic accuracy which reduces the scanning time compared to the conventional one. However, synthetic T2-FLAIR images need to be improved.

Delineation of MidXq28-duplication syndrome distal to MECP2 and proximal to RAB39B genes.

Two distinct genomic disorders have been linked to Xq28-gains, namely Xq28-duplications including MECP2 and Int22h1/Int22h2-mediated duplications involving RAB39B. Here, we describe six unrelated patients, five males and one female, with Xq28-gains distal to MECP2 and proximal to the Int22h1/Int22h2 low copy repeats. Comparison with patients carrying overlapping duplications in the literature defined the MidXq28-duplication syndrome featuring intellectual disability, language impairment, structural brain malformations, microcephaly, seizures and minor craniofacial features. The duplications overlapped for 108 kb including FLNA, RPL10 and GDI1 genes, highly expressed in brain and candidates for the neurologic phenotype.

Abnormal cervical lymph nodes in multiple sclerosis: a preliminary ultrasound study.

BACKGROUND: Cervical lymph nodes are the first drainage stations of the brain and therefore play a key role in neuroinflammatory disorders such as multiple sclerosis. OBJECTIVE: The aim of this study was to evaluate, by using ultrasound imaging, cervical lymph nodes in patients with multiple sclerosis and to ascertain if such patients have any clinical features to attest their role. METHODS: We enrolled 43 patients affected by relapsing-remitting multiple sclerosis (22 drug free and 21 under treatment with natalizumab or fingolimod), who underwent ultrasound examination. The morphology, diameters and volume of cervical lymph nodes were measured. We evaluated also a control group of 20 healthy volunteers. RESULTS: Between-group comparisons showed that the mean anteroposterior diameters in the cervical lymph nodes on both sides of the neck were significantly different (χ 2 = 19.5, p < 0.001 for right; χ 2 = 20.0, p < 0.001 for left). Post hoc contrasts showed that the mean anteroposterior diameters were greater both in drug-naive (mean ± SD 0.66 ± 0.20 cm; p < 0.001) and treated patients (0.55 ± 0.24 cm; p < 0.001) compared to healthy individuals (0.36 ± 0.19 cm). Moreover, significant difference (p < 0.001) was shown on comparing the mean volume of the cervical lymph nodes on both sides of the neck in the studied groups. No significant differences emerged between the drug-free and treated patients. CONCLUSION: The abnormalities shown by ultrasound in cervical lymph nodes are related to deep ones and independent of the ongoing treatment, suggesting a relationship between lymphatic drainage and disease pathology.

Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers.

INTRODUCTION: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. METHODS: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). RESULTS: We found a positive association between CSF α-syn concentrations and brain ß-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. DISCUSSION: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and ß-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aß1-42, total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40.

INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid ß peptide [i.e., Aß1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation. METHODS: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified. RESULTS: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid ß peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for distinguishing between FTD patients and HC (AUROC = 0.78). CONCLUSIONS: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.

Inappropriateness of diagnostic imaging examinations in the inpatient setting: a case study research.

OBJECTIVE: The purpose of our study was to audit the clinical appropriateness of the prescriptions of whole body CT (WB-CT), PET-CT and chest X-rays (CXRs) performed at Tor Vergata University Hospital in the inpatient setting. MATERIALS AND METHODS: WB-CT, PET-CT and CXRs examinations were retrospectively analysed in the period between January and December 2014. CXR examinations were divided into bedside CXRs and traditional CXRs. The appropriateness of the examinations was defined according the American College of Radiology Appropriateness Criteria. Inappropriate examinations were divided into six inappropriateness categories in accordance with the European Union Medical Imaging Guidelines. RESULTS: Appropriateness was suboptimal for all analysed techniques CXRs (A = 38%, I = 62%); bedside CXRs (A = 45%, I = 53%); WB-CT (A = 45%, I = 55%); PET-CT (A = 48%, I = 52%). With respect to WB-CT the highest rate of inappropriate imaging prescriptions came from the haematology clinical operative unit (OU) (44%) and emergency medicine (33%); with respect to PET-CT, the thoracic surgery OU (53%) and haematology OU (48%) showed the most inappropriate prescriptions. For CXRs, the percentage of inappropriateness was consistently distributed among all surgical OUs. For bedside CXRs, the largest inappropriate prescribers were the emergency medicine OU (48%), the cardiac surgery OU (58%), the intensive care OU (67%) and anaesthesia resuscitation OU (78%). The most represented classes of inappropriateness were 2, 3, 4 and 6. CONCLUSIONS: The elimination of inappropriate prescriptions would result in an annual savings of approximately 390,000 Euro. An implementation plan to increase prescription appropriateness is under development by our group.