Machine Learning Model to Predict Diagnosis of Mild Cognitive Impairment by Using Radiomic and Amyloid Brain PET.

PURPOSE: The study aimed to develop a deep learning model for predicting amnestic mild cognitive impairment (aMCI) diagnosis using radiomic features and amyloid brain PET. PATIENTS AND METHODS: Subjects (n = 328) from the Alzheimer's Disease Neuroimaging Initiative database and the EudraCT 2015-001184-39 trial (159 males, 169 females), with a mean age of 72 ± 7.4 years, underwent PET/CT with 18 F-florbetaben. The study cohort consisted of normal controls (n = 149) and subjects with aMCI (n = 179). Thirteen gray-level run-length matrix radiomic features and amyloid loads were extracted from 27 cortical brain areas. The least absolute shrinkage and selection operator regression was used to select features with the highest predictive value. A feed-forward neural multilayer network was trained, validated, and tested on 70%, 15%, and 15% of the sample, respectively. Accuracy, precision, F1-score, and area under the curve were used to assess model performance. SUV performance in predicting the diagnosis of aMCI was also assessed and compared with that obtained from the machine learning model. RESULTS: The machine learning model achieved an area under the receiver operating characteristic curve of 90% (95% confidence interval, 89.4-90.4) on the test set, with 80% and 78% for accuracy and F1-score, respectively. The deep learning model outperformed SUV performance (area under the curve, 71%; 95% confidence interval, 69.7-71.4; 57% accuracy, 48% F1-score). CONCLUSIONS: Using radiomic and amyloid PET load, the machine learning model identified MCI subjects with 84% specificity at 81% sensitivity. These findings show that a deep learning algorithm based on radiomic data and amyloid load obtained from brain PET images improves the prediction of MCI diagnosis compared with SUV alone.

Application of Artificial Intelligence in the Analysis of Features Affecting Cataract Surgery Complications in a Teaching Hospital.

Aims: To evaluate the ocular and systemic factors involved in cataract surgery complications in a teaching hospital using artificial intelligence. Methods: One eye of 1,229 patients with a mean age of 70.2 ± 10.3 years old that underwent cataract surgery was selected for this study. Ocular and systemic details of the patients were recorded and then analyzed by means of artificial intelligence. A total of 1.25 billion simulations of artificial intelligence learning and testing were conducted on several variables and a customized model of analysis was developed. Results: A total of 73 complications were recorded in this study. According to the analysis performed, the main factors involved in cataract surgery complications were: a surgeon in training, axial length and intraocular lens power. The model predicted how long surgery would last with an error of <6 min compared to the effective time needed. Conclusions: According to the data here obtained, artificial intelligence could be an interesting option to build customized models able to prevent complications and to predict actual surgery time. The customized algorithm option allows the development of better models adaptable to different units as well as the possibility to be calibrated for the same unit along time.

Bergmeister's papilla in a young patient with type 1 sialidosis: case report.

BACKGROUND: Sialidosis is a rare genetic lysosomal storage disorder caused by a deficit of neuraminidase enzyme activity. Patients with sialidosis present various neurological disorders such as: myoclonic epilepsy and hypotonia, often associated with visual impairment. A typical aspect of sialidosis is the finding of a macular cherry-red spot on ocular fundus examination. In this paper we describe a unilateral case of Bergmeister's papilla (BP) in a young female patient suffering from type 1 sialidosis. CASE PRESENTATION: A 28-year-old young woman suffering from type 1 sialidosis, confirmed by previously described compound heterozigosity Leu91Arg and Gly328Ser on N-acetyl-alpha-neuraminidase - 1 (NEU1) gene, underwent an opthalmological examination at the Eye Clinic of the University of Campania L. Vanvitelli, for bilateral visual deterioration. The patient was suffering from myoclonic epilepsy with hypotonia and severe motor disability. Fundoscopic examination showed a typical macular cherry-red spot with retinal pigment epithelium dystrophy in the middle periphery, in both eyes. Furthermore, in the left eye (OS), a vitreous thickening was observed in the nasal sector of the optic disc, remnant of fetal vasculature on the optic disc (Bergmeister's papilla). Optical coherence tomography (OCT) showed, in both eyes, a thickening of the ganglion cell layer (GCL) with a hyperreflective opacity as a cap on the left optic disc. CONCLUSIONS: In our paper we have described, for the first time in literature, a case of BP in a patient with type 1 sialidosis. The detection of BP with thickening of the peripapillary vitreous by SD-OCT is useful in monitoring any vitreo-retinal change that could cause future visual deterioration.

Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients.

PURPOSE: The extent of amyloid burden associated with cognitive impairment in amnestic mild cognitive impairment is unknown. The primary aim of the study was to determine the extent to which amyloid burden is associated to the cognitive impairment. The secondary objective was to test the relationship between amyloid accumulation and memory or cognitive impairment. MATERIALS AND METHODS: In this prospective study 66 participants with amnestic mild cognitive impairment underwent clinical, neuropsychological and PET amyloid imaging tests. Composite scores assessing memory and non-memory domains were used to identify two clinical classes of neuropsychological phenotypes expressing different degree of cognitive impairment. Detection of amyloid status and definition of optimal amyloid ± cutoff for discrimination relied on unsupervised k-means clustering method. RESULTS: Threshold for identifying low and high amyloid retention groups was of SUVr = 1.3. Aß + participants showed poorer global cognitive and episodic memory performance than subjects with low amyloid deposition. Aß positivity significantly identified individuals with episodic memory impairment with a sensitivity and specificity of 80 and 79%, (χ2 = 21.48; P < 0.00001). Positive and negative predictive values were 82 and 76%, respectively. Amyloid deposition increased linearly as function of memory impairment with a rate of 0.13/ point of composite memory score (R = -44, P = 0.0003). CONCLUSION: The amyloid burden of SUVr = 1.3 allows early identification of subjects with episodic memory impairment which might predict progression from MCI to Alzheimer's disease. TRIAL REGISTRATION: EudraCT 2015-001184-39.

Increased incidence of axonal Guillain-Barré syndrome in La Spezia area of Italy: A 13-year follow-up study.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy with a worldwide incidence of 0.81-1.89 per 100 000 person-years. In Europe and North America only 5% of patients with GBS have axonal subtypes, which in South America and Asia account for 30%-47% of cases. The aim of our study is to assess the annual incidence and clinical features of GBS in La Spezia area in Italy. A retrospective (from 1 January 2003 to 31 December 2011) followed by a prospective (from 1 January 2012 to 31 December 2015) analysis was carried out on patients admitted to La Spezia hospital who fulfilled the GBS diagnostic criteria. A total of 86 patients (58 men), mean age of 62.7 years (range 21-90), were included. The mean annual incidence rate was 3/100 000 (range: 0.9/100 000-5.37/100 000) significantly higher than the European incidence (P < 0.001). Forty-seven percent were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 35% as acute motor and motor-sensory axonal neuropathy (AMAN-AMSAN), 13% as variant forms, and 5% were not defined. AIDP was most common in "Golfo dei Poeti" (50%) and "Val di Magra" (63.2%), whereas AMAN/AMSAN prevailed in "Val di Vara" (63.6%) and "Riviera Spezzina" (62.5%) (P = 0.024). In La Spezia area GBS incidence (especially the AMAN subtype) is significantly higher than the incidence reported in Europe. AIDP predominates in the eastern area whereas AMAN/AMSAN in the western, with a significantly different incidence rate (P = 0.003). Prospective studies to assess possible predisposing environmental factors are needed.

Changes in clinical management and diagnosis following DaTscan SPECT imaging in patients with clinically uncertain parkinsonian syndromes: a 12-week follow-up study.

BACKGROUND: An accurate diagnosis is important for timely and adequate treatment in patients with clinically uncertain parkinsonian syndrome (CUPS). OBJECTIVE: The objective of this study was to assess safety and changes in clinical management, diagnosis and quality of life (QoL) at 4 and 12 weeks following DaTscan (ioflupane [(123)I] injection) imaging in patients with CUPS. METHODS: This randomized, open-label, single-dose, multicenter trial was carried out in patients with CUPS who were randomized to either a DaTscan imaging group or to a control group without imaging. The main outcome measures were the proportions of patients with changes in clinical management and diagnosis from baseline through to 12 weeks after DaTscan. A total of 19 university hospital centers in Europe and the USA participated in the study. There were 267 patients enrolled and randomized (131 DaTscan, 136 control). RESULTS: Significantly more DaTscan patients had changes in clinical management after 12 weeks (p = 0.004) compared to the control group, and significantly more DaTscan patients had changes in diagnosis at 4 weeks and at 12 weeks (both p < 0.001) compared to control patients. No significant difference in total score for QoL was observed between groups during the study duration. DaTscan was safe and well-tolerated. No deaths, serious adverse events (AEs) or withdrawals due to AEs occurred during the study. One patient had a headache following treatment with a suspected relationship to DaTscan. CONCLUSION: DaTscan imaging significantly affected the clinical management and diagnosis of patients with CUPS. DaTscan is safe and well-tolerated and is a useful adjunct to differential diagnosis of CUPS.

Resting state in Alzheimer's disease: a concurrent analysis of Flash-Visual Evoked Potentials and quantitative EEG.

BACKGROUND: To investigate to what extent Alzheimer's Disease (AD) affects Resting State activity, the possible impairment of independent electrophysiological parameters was determined in Eye-open and Eye-closed Conditions. Specifically, Flash-Visual Evoked Potential (F-VEP) and quantitative EEG (q-EEG) were examined to establish whether abnormalities of the former were systematically associated with changes of the latter. METHODS: Concurrently recorded F-VEP and q-EEG were comparatively analysed under Eye-open and Eye-closed Conditions in 11 Controls and 19 AD patients presenting a normal Pattern-Visual Evoked Potential (P-VEP). Between Condition differences in latencies of P2 component were matched to variations in spectral components of q-EEG. RESULTS: P2 latency increased in 10 AD patients with Abnormal Latency (AD-AL) under Eye-closed Condition. In these patients reduction of alpha activity joined an increased delta power so that their spectral profile equated that recorded under Eye-open Condition. On the opposite, in Controls as well as in AD patients with Normal P2 Latency (AD-NL) spectral profiles recorded under Eye-open and Eye-closed Conditions significantly differed from each other. At the baseline, under Eye-open Condition, the spectra overlapped each other in the three Groups. CONCLUSION: Under Eye-closed Condition AD patients may present a significant change in both F-VEP latency and EEG rhythm modulation. The presence of concurrent changes of independent parameters suggests that the neurodegenerative process can impair a control system active in Eye-closed Condition which the electrophysiological parameters depend upon. F-VEP can be viewed as a reliable marker of such impairment.

Impact of DaTscan SPECT imaging on clinical management, diagnosis, confidence of diagnosis, quality of life, health resource use and safety in patients with clinically uncertain parkinsonian syndromes: a prospective 1-year follow-up of an open-label controlled study.

BACKGROUND: This study assessed the impact of DaTscan on clinical management, diagnosis, confidence of diagnosis (CoD), quality of life (QoL), health resource use (HRU) and safety during a 1-year follow-up in patients with clinically uncertain parkinsonian syndromes (CUPS). METHODS: A total of 19 university hospital centres in Europe and the USA participated in this open-label, single-dose, prospective, clinical trial in patients with CUPS who were randomised to a DaTscan imaging group or to a no-imaging (control) group. The proportion of patients with changes in clinical management, diagnosis, CoD, QoL and HRU from baseline through 1 year post-DaTscan was compared between groups. RESULTS: There were 273 patients randomised (135 DaTscan, 138 control). Significantly more patients in the DaTscan imaging group had at least one change in their actual clinical management after 12 weeks (p=0.002) and after 1 year (p<0.001) compared with patients in the control group. In addition, significantly more DaTscan patients had changes in diagnosis and an increased CoD at 4 weeks, 12 weeks and 1 year (all p<0.001) compared with control patients. No significant differences in total score for QoL or HRU were observed between groups during the 1-year follow-up period. DaTscan was safe and well tolerated. One patient in the imaging group had an adverse event (headache) with suspected relationship to DaTscan post-administration. CONCLUSIONS: DaTscan had a significant impact on clinical management, diagnosis and CoD in patients with CUPS. DaTscan is safe and well tolerated, and is a useful adjunct to differentiate a diagnosis of CUPS. Trial registration number http://ClinicalTrials.gov Identifier: NCT00382967.

Molecular detection of human mammaglobin in cerebrospinal fluid from breast cancer patient with leptomeningeal carcinomatosis.

Leptomeningeal (LM) carcinomatosis is an increasing clinical complication in patients with advanced breast cancer (BC). The LM carcinomatosis diagnostic procedures rely mainly on cerebrospinal fluid (CSF) cytology, although both the amount of CSF and the number of malignant cells remain limiting factors. Therefore, efforts should be made to design new highly sensitive diagnostic tools to detect malignant cells in CSF of BC patients with LM carcinomatosis. In this study, the human Mammaglobin (hMAM) mRNA amplification by RT-PCR was employed to detect metastatic cells in CSF and thus, to diagnose LM carcinomatosis in a BC patient. Our data demonstrate that hMAM transcripts are expressed in the CSF of a BC patient with LM carcinomatosis, hence making RT-PCR for hMAM a potentially suitable test to identify occult BC cells in the brain.

Changing spectrum and outcome of 705 fetal congenital heart disease cases: 12 years, experience in a third-level center.

INTRODUCTION: Congenital heart diseases are the most common prenatal and postnatal malformations. Nowadays, fetal echocardiography is a widely practiced technique; however, the impact of prenatal diagnosis on prognosis of the newborns affected by congenital heart disease remains uncertain. OBJECTIVE: To assess the outcome and the changes in the spectrum of prenatally detected congenital heart disease in our tertiary care centre in 12 years of activity (1995-2006). METHODS AND RESULTS: We detected 705 congenital heart diseases: 32% (223) were associated with extracardiac or chromosomal anomalies or both, and 68% (482) were isolated. Termination of pregnancy was chosen in 81% for associated anomalies and 37% for isolated anomalies (P<0.001). Of these, more than one-third occurred in hypoplasic left heart cases. The general survival rate was 72%; it was significantly lower in the group with associated heart diseases (46 vs. 80%, P<0.001). Over 12 years we noticed a reduction in the number of multimalformed fetuses and of the hypoplasic left heart cases, and a higher number of aortic arch anomalies detected. During the past 6 years of activity the survival rate obtained has significantly increased (55 to 84%, P<0.05), the termination rate has significantly decreased (35 to 14%, P<0.001) and the number of neonatal deaths has significantly decreased (39 to 10%, P<0.001). CONCLUSION: The survival and the voluntary termination of fetuses with prenatally detected congenital heart diseases are strongly influenced by disease severity and by associated extracardiac or chromosomal anomalies, or both. Over 12 years, the spectrum of fetal congenital heart disease has changed and their outcome has significantly improved.

Two-dimensional strain to assess regional left and right ventricular longitudinal function in 100 normal foetuses.

AIMS: Previous reports have demonstrated that myocardial velocities are not sufficiently sensitive in foetal heart studies. Strain (S) imaging is a new non-invasive ultrasonic technique able to quantify regional myocardial deformation properties. Strain imaging has a superior sensitivity than myocardial velocity for non-invasive assessment of ventricular function. However, Doppler-derived strain imaging has been used to quantify myocardial deformation properties in the foetal heart with rather limited results, because of angle dependency, sensitivity to extracardiac movement, the need for good-quality images, long and time-consuming post-processing and the low reproducibility of Doppler-derived strain. Recently, a novel method for motion estimation based on two-dimensional (2D) tissue tracking strain (2D-S) echocardiography using time-domain processing has been developed, providing rapid assessment of regional myocardial strain that is independent of both cardiac translation and angle dependency, with a very good reproducibility. However, no information on 2D-S in human foetuses has so far been provided. METHODS: We studied 100 consecutive normal foetuses (gestation range: 20-32 weeks; no evidence of structural cardiovascular disease by 2D echo and Doppler study) using 2D-S imaging. Left ventricle (LV) and right ventricle (RV) peak myocardial negative strain values were obtained. RESULTS: Strain data were obtained from all the studied subjects, the duration of post processing was 3 +/- 2 min for each patient dataset. Peak longitudinal deformation parameters were homogeneous in all the three studied walls (strain: septum = -25 +/- 5%; lateral wall = -25 +/- 4%; RV free wall = -24 +/- 4%; P = NS). There were significant correlations between gestational age and peak longitudinal strain (P < 0.001; R: -0.73). Inter and intra-observer variability for strain was good, <3 and <6%, respectively. CONCLUSION: This study demonstrated that 2D-S is a feasible and reproducible approach to assess regional ventricular function in the foetal heart, ready for the clinical application.

Vertebral artery dissection onset mimics migraine with aura in a graphic designer.

Headache is the most common symptom in patients with cervical artery dissection. This symptom, however, rarely occurs in isolation, and more commonly is associated with other neurological symptoms and signs. Visual symptoms associated with vertebral artery dissection (VD) have also been observed, but do not typically mimic the migraine aura. Here, we report a young patient who presented VD, embolic ischemic lesions, and visual symptoms with the features of aura, followed by migraine headache. The suggestion of VD dissection should be kept in mind in those cases complaining of the first attack of headache that mimics migraine with aura. In these cases, an extensive neuroimaging study is advisable.

The challenge of fetal dysrhythmias: echocardiographic diagnosis and clinical management.

OBJECTIVE: The present study aimed to evaluate the management of fetal cardiac dysrhythmias based on prior identification of the underlying electrophysiological mechanism. METHODS: We studied 36 consecutive fetuses with cardiac dysrhythmia. Rhythm diagnosis was based on M-mode, pulsed wave Doppler and tissue Doppler imaging (TDI). Only fetuses with: (i) incessant tachycardia (> 12 h) and mean ventricular rate > 200 beats/min, (ii) signs of left ventricular dysfunction, or (iii) hydrops, were treated using oral maternal drug therapy. RESULTS: The mean gestational age at diagnosis was 24.3 +/- 4.5 weeks. Twenty-one fetuses had tachycardia with a 1: 1 atrial-ventricular (AV) conduction. Based on ventricular-atrial interval, prenatal diagnosis was: permanent junctional reciprocating (n = 6), atrial ectopic (n = 6) or atrial-ventricular re-entry tachycardia (n = 9). One had atrial flutter, one ventricular tachycardia and four congenital AV block. Nine showed premature atrial or ventricular beats. Fifteen fetuses with incessant tachycardia, left ventricular dysfunction or hydrops were prenatally treated with maternal administration of digoxin, sotalol or flecainide. The total success rate (sinus rhythm or rate control) was 14/15 (93%). Seven fetuses were hydropics. Three of these died (one at 28 weeks of gestation, two in the first week of life). The prenatal diagnosis of dysrhythmia was confirmed at the birth in 31 of 35 live-born. No misdiagnosis was made using TDI. At 3 +/- 1.1-year follow-up, 33/35 children were alive and well. CONCLUSIONS: Fetal echocardiography could clarify the electrophysiological mechanism of fetal cardiac dysrhythmias and guide the therapy.

The 'in-plane' view of the inter-ventricular septum. A new approach to the characterization of ventricular septal defects in the fetus.

OBJECTIVES: Objectives of this study are (1) to describe how to obtain the in-plane view of the inter-ventricular septum, (2) to assess its feasibility in a population of fetuses referred for fetal echocardiography, (3) to demonstrate its effectiveness in the characterization of VSD in the fetus. METHODS: The in-plane view of the inter-ventricular septum is conducted in a plane almost perpendicular to that of the long axis of the left ventricle, tilting the transducer towards the right ventricle, paying attention not to 'enter' the right ventricular chamber. Its feasibility has been assessed in 41 fetuses referred for fetal echocardiography, by recording the visualization/failure rates by fetal lie and acoustic window. The in-plane view of the inter-ventricular septum was then employed in healthy fetuses and diseased fetuses with VSDs. RESULTS: The success rates in obtaining the in-plane view of the inter-ventricular septum was dependent upon fetal lie; visualization rates were 100, 36 and 0% in case of posterior, lateral and anterior spine, respectively. When used in the anatomic characterization of VSDs, this view provided significant additional information. CONCLUSIONS: The in-plane view of the inter-ventricular septum represents a new echocardiographic view that can be used to enhance the assessment of the inter-ventricular septum of the fetal heart. Its use should be considered whenever the presence of a VSD is suspected during fetal echocardiography, and in these cases it often provides additional information.

Prenatal ultrasonographic findings of a cardiac myxoma.

BACKGROUND: Cardiac myxomas have been reported in the neonate but never in the fetus. We present the prenatal diagnosis of such a tumor. CASE: The patient had been referred for fetal echocardiography for a right atrial mass. At 23 weeks' gestation, the tumor was initially located in the left atrium. Then it crossed the foramen ovale and began moving between the right atrium and ventricle. It appeared as a soft, moderately echogenic mass with a long peduncle attached to the right atrial wall. It was followed until delivery and removed at 20 days of life. CONCLUSION: This case shows that myxomas can also arise in the fetus. Such a diagnosis should be taken into consideration when a soft, echogenic, pedunculated mass is seen within the fetal heart.

Prenatal ultrasound diagnosis of Toriello-Carey syndrome.

Toriello-Carey syndrome is a rare malformative complex, described for the first time in 1988, characterized by agenesis of the corpus callosum, facial anomalies, cardiac defects and hypotonia. Relatively few neonatal cases have been reported. We describe here the first prenatal ultrasound diagnosis of the syndrome based on the detection of agenesis of the corpus callosum and spongious cardiomyopathy in a 22-week-old fetus of a couple with positive family history. The first sib of the couple was diagnosed with Toriello-Carey syndrome at 1 year of age, and had, in addition to the typical facial anomalies not detectable by ultrasound, agenesis of the corpus callosum and the same heart lesion (spongious cardiomyopathy). This report demonstrates that prenatal diagnosis of Toriello-Carey syndrome is feasible in the second trimester of pregnancy.