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Spinal trauma is an important cause of disability worldwide. Injury to the cervical spine (CS) occurs frequently after major trauma. 5–10% of patients with blunt trauma have a cervical spine injury. The cervical spine accounts for ~ 50% of all spinal injuries. Determination of CS stability is a common challenge in the acute care setting of patients with trauma. Several issues, indeed, are of particular concern: who needs CS imaging; what imaging should be obtained; when should computed tomography (CT), magnetic resonance imaging (MRI), or flexion/extension (F/E) radiographs be obtained; and how is significant ligamentous injury excluded in the comatose patient. CT and MRI both have roles to play. This article aims to present the different imaging to frame techniques to be used with greater precision in the acute event also for the purpose of planning the next therapeutic process. An overview of the applicability of the same methods in forensic pathology is also provided highlighting possible future biomarker to ease in diagnosis of acute TBI.

Introduction: Correct perioperative management of anticoagulant therapy is essential to prevent thromboembolic events and reduce the risk of bleeding. The lack of universally accepted guidelines makes perioperative anticoagulant therapy management difficult. The present study aims to identify the perioperative risks of oral anticoagulant therapy and to reduce adverse events through Failure Mode and Effect Analysis (FMEA). Materials and Methods: A multidisciplinary working group was set up, and four main phases of the process were identified. Each of these phases was divided into micro-activities to identify the related possible failure modes and their potential consequences. The Risk Priority Number was calculated for each failure mode. Results and Discussion: Seventeen failure modes were identified in the entire perioperative period; those with a higher priority of intervention concern the incorrect timing between therapy suspension and surgery, and the incorrect assessment of the bleeding risk related to the invasive procedure. Conclusion: The FMEA method can help identify anticoagulant therapy perioperative failures and implement the management and patient safety of surgical procedures.

Background: In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI. Methods: To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process. Discussion and conclusion: The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.

The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health.A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review.Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a "cytokine storm".The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.

Haemodialysis (HD) is one of the methods for renal replacement therapy in the management of advanced chronic kidney disease through an osmosis process that allows purification of blood in the dialysis machine. The complexity of the dialytic procedure often requires the presence of a multi-specialist, multi-disciplinary team. The dialysis process is an important target for clinical risk management. Failure Mode and Effect Analysis (FMEA) is a proactive technique, considered a purposeful and dynamic tool for clinical risk management. FMEA is noted in five phases that allow a preliminary assessment of a definite process through identification and classification of risk priorities. This study represents the first of a two-phase project where FMEA is applied to HD in the setting of San Feliciano Hospital. The dialysis center performs ~12,000 dialysis sessions per year. The dialysis process is divided into different stages. A total of 31 failure modes were identified in the whole dialysis stages; more than 2/3 of the failure modes were related to the only connecting of the patient to the dialysis machine. The first phase of the study clearly remarked that the most critical step of the dialytic process is represented by the connection between the patient and the machine, as expected. Indeed, in order to have the dialysis set up, an arteriovenous fistula must be surgically created prior to the procedure and it is one of the most important issues in the HD process because of the necessity of a constant revision of it. FMEA application to HD is a useful tool, easy to be implemented and it is likely to nimbly reveal the practical and potential solutions to the critical steps of the procedure.

Background: Traumatic brain injury (TBI) can be considered a "silent epidemic", causing morbidity, disability, and mortality in all age cohorts. Therefore, a greater understanding of the underlying pathophysiological intricate mechanisms and interactions with other organs and systems is necessary to intervene not only in the treatment but also in the prevention of complications. In this complex of reciprocal interactions, the complex brain-gut axis has captured a growing interest. Aim: The purpose of this manuscript is to examine and systematize existing evidence regarding the pathophysiological processes that occur following TBI and the influences exerted on these by the brain-gut axis. Methods: A systematic review of the literature was conducted according to the PRISMA methodology. On the 8th of October 2021, two independent databases were searched: PubMed and Scopus. Following the inclusion and exclusion criteria selected, 24 (12 from PubMed and 12 from Scopus) eligible manuscripts were included in the present review. Moreover, references from the selected articles were also updated following the criteria mentioned above, yielding 91 included manuscripts. Results: Published evidence suggests that the brain and gut are mutually influenced through four main pathways: microbiota, inflammatory, nervous, and endocrine. Conclusion: These pathways are bidirectional and interact with each other. However, the studies conducted so far mainly involve animals. An autopsy methodological approach to corpses affected by traumatic brain injury or intestinal pathology could represent the keystone for future studies to clarify the complex pathophysiological processes underlying the interaction between these two main systems.

Penetrating cardiac injuries represent an increasingly frequent type of trauma in clinical and autopsy practice. The present study aims to review the specialist literature of the last decade (2010-2020) to assess whether the main features of these lesions have changed compared to previous years. The following characteristics were considered: sex, age, cardiac structure involved, execution or not of surgery and postoperative survival, hemodynamic stability, circumstances and mechanism of production, injury and cause of death. Furthermore, the authors propose a practical appraisal of penetrating heart injury in which death was due to a delay in rescue. In line with the data obtained from the practical case, the review showed that compared to the past, the differences concern especially the mortality rate. This paper highlights that the forensic pathologist who approaches a case of transcardiac injury must consider that the circumstances of death are not always attributable to accidental events, attacks or suicides, but may also be due to clinical malpractice or failure to rescue.

Crime scene investigation should be carried out using a critical forensic approach by an expert team. This provides essential tools in the research and collection of evidence and samples which must be integrated with the autopsy and the police officers’ investigations. This paper aims to highlight the importance of a multidisciplinary approach to crime scene investigation and describes a very interesting criminal case. As demonstrated by this case, the evidence obtained from the crime scene analysis sheds light on difficult cases, such as murders staged as suicides or accidents.

Background Self-defense is legitimate both in common law and in civil law systems. Nevertheless, there remains the age-old question for the prosecutor to identify the limit between the righteous self-defense and the self-defense with excessive force. In these cases, the gathering of all evidence by a forensic multidisciplinary team is essential to provide the necessary data for the prosecutor’s evaluation. Case presentation The case of a 55-year-old man who was killed in front of his neighbor’s house is described. The prosecutor alerted the forensic team, classifying the crime as a gunshot homicide. The neighbor immediately admitted his responsibility as self-defense. Moreover, the relatives of the victim told a different version of the story, assuring that the neighbor had killed him for futile motivations. For these reasons, the prosecutor established further investigations, such as autopsy, the K-9 unit exploration, and alerting the forensic biologist for analysis. Conclusions This case aims to highlight the teamwork of multidisciplinary forensic expertise to solve complex cases; moreover, combining ultra-specialist forensic activities, such as the K-9 unit, it is possible to collect all the evidence to submit to the prosecutor for the formulation of judgment.

Dog attacks today represent a health hazard considering that prevention strategies have not always been successful. The identification of the dog that attacked the victim is necessary, considering the civil or criminal consequences for the animal's owner. An accurate scene analysis must be performed collecting a series of important information.Forensic investigations in dog attacks involve different methods, such as the evaluating of the canine Short Tandem Repeat (STR) typing in saliva traces on wounds or bite mark analysis, however, these techniques cannot always be applied. The effort to find new methods to identify the dog that attacked the victim represents a very interesting field for the forensic community.This study aims to propose an innovative approach, based on the identification of the victim's profile in the dog's mouth, using a buccal swab on the suspected aggressor dog, to find the victim's genetic profile. In addition, a further goal of this study is to determine the persistence time of hexogen DNA in the dog's mouth to define a timeframe for performing this particular technique.For this purpose, ten different dogs were used to aggressively bite a bovine sample (reference sample) to simulate the victim. For each dog two buccal swabs were taken at different time intervals: 30', 45', 60', 90', 120', 150', 180' and 240'. The typing of the swabs provided an interpretable profile after 45' while traces of bovine profile were found until 150' after the dog attack simulation.These results could be improved using the human identification kit, which is more sensitive. In the light of this experimental study, the forensic community should consider using this approach in real casework studies with the aim of collecting new data, validating this technique for forensic use. (C) 2020 Elsevier B.V. All rights reserved.

Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. We found that SM levels mirror both peripheral myelination during development and small myelin rearrangements in experimental models. As in acquired demyelinating peripheral neuropathies myelin breakdown occurs, SM amount in the CSF of these patients might detect the myelin loss. Indeed, quantification of SM in 262 neurological patients showed a significant increase in patients with peripheral demyelination (p = 3.81 * 10 − 8) compared to subjects affected by non-demyelinating disorders. Interestingly, SM alone was able to distinguish demyelinating from axonal neuropathies and differs from the principal CSF indexes, confirming the novelty of this potential CSF index. In conclusion, SM is a specific and sensitive biomarker to monitor myelin pathology in the CSF of peripheral neuropathies. Most importantly, SM assay is simple, fast, inexpensive, and promising to be used in clinical practice and drug development.

A subtle cognitive impairment can be detected early in the course of Parkinson's disease (PD). Executive, memory and visuospatial functions are specifically affected, but the underlying pathophysiological basis is not well elucidated yet and may be heterogeneous. The recent identification of a PD-related cognitive metabolic pattern (PDCP), including hypometabolism in associative frontal, parietal and posterior limbic structures, has integrated the classical notion of a striato-frontal syndrome at the basis of cognitive dys-function. Recent evidence suggests that whilst executive dys-function is seen in virtually all PD patients, visuospatial and memory impairment may share a higher risk for the subsequent development of dementia. By means of perfusion SPECT and [18F]FDG-PET, cortical dys-function may be highlighted since the early stages, it is more evident in PD patients with Mild Cognitive Impairment (MCI), and reaches the maximum in PD dementia (PDD). Posterior temporo-parieto-occipital dys-function in associative and limbic cortex, closely resembling that found in Alzheimer's disease patients, is found in PDD, with a more severe occipital hypometabolism and a relatively milder hypometabolism in medial temporal lobe structures. Furthermore, deficit of acetylcholinesterase (AchE) can be found by means of [11C]MP4A-PET already in early stage of PD, especially in posterior regions, then becoming more severe in PDD and in dementia with Lewy bodies (DLB). Administration of AchE inhibitors to PDD patients increased brain metabolism in bilateral frontal and left parietal regions, and left posterior cingulate. Finally, the recent availability of radiopharmaceuticals able to disclose amyloid brain deposition has allowed to demonstrate amyloid load in a part of patients with PDD, possibly due to diffuse rather than neuritic plaques. Brain PET and SPECT have strongly contributed to the understanding of the pathophysiology of cognitive impairment in PD and may serve as probes to monitor the effects of therapeutic interventions.

The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.

Introduction The association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD. Methods Thirty-eight de novo , drug naive PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, 123 I-FP-CIT-SPECT and 18 F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD. Results On first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015). Conclusions PD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.

Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's alpha: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients.

Purpose The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available. Methods We retrospectively selected 25 patients with lateonset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). Results Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD- patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule. Conclusion These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.

Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer’s disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT , GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU , CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1 , PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer’s and non-Alzheimer’s forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalenceof AD in the femalepopulation compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area.

An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs) in each hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine (SVM) and the AAL VOIs was tested against a validated method (PALZ). At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed., Highlights • 18F-FDG-PET/CT analysis of metabolic differences between MCI converting to AD and HC • Large and very well controlled cohorts from EADC-Consortium were investigated. • Data were analyzed by a friendly-to-use Matlab-based script and Support Vector Machine. • Excellent discrimination between MCI and HC (sensitivity 92%; specificity 91%) • Highest accuracy reported so far in MCI and promising implementation in clinical routine

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) can be induced by antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of the serotonergic system in the pathogenesis of RBD has been proposed. However, the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We aimed to study brain stem serotonergic system integrity, by means of (123)I-FP-CIT-SPECT, in a group of iRBD patients as compared to normal subjects. DESIGN: Single-center, prospective observational study. SETTING: University hospital. PATIENTS OR PARTICIPANTS: Twenty iRBD outpatients and 23 age-matched normal controls. MEASUREMENTS AND RESULTS: The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT-SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT-SPECT images were analyzed and compared between iRBD patients and controls by means of both region of interest analysis at basal ganglia, midbrain, pons and thalamus levels, and voxel-based analysis, taking into account age and the use of SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to nondisplaceable binding ratios (SBR) values was found between iRBD and normal subjects at brainstem and thalamus levels while iRBD patients showed lower SBR values in all basal ganglia nuclei (P < 0.0001) compared to controls. CONCLUSIONS: These results suggest that the serotonergic system is not directly involved in RBD pathogenesis while confirming nigro-striatal dopaminergic deafferentation in iRBD.

Forty-nine consecutive, drug naive outpatients with de novo Parkinson's disease (PD) and 12 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) underwent clinical examination and dopamine transporter single photon emission computed tomography with [(123)I]-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane as a biomarker of nigro-striatal function. PD patients were grouped into rapid eye movement sleep behavior disorder (RBD) negative (PD-RBD-) and RBD positive (PD-RBD+). Repeated measures and univariate analysis of variance were used to compare dopaminergic and clinical impairment among groups. The variations of dopamine transporter-single photon emission computed tomography specific binding ratios (SBR) as a function of group belonging were significantly different (p = 0.0013) at caudate with respect to putamen level. Indeed, putamen SBR progressively decreased from iRBD to PD-RBD- and PD-RBD+ groups while caudate SBR were higher in PD-RBD- group than in PD-RBD+ and even than in iRBD group. Motor impairment was more severe in PD patients with RBD than in those without RBD. Our data suggest that a more severe nigro-caudate dopaminergic deafferentation is related to RBD, both in its idiopathic form and in PD patients.

The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain(18)F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance.The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score.Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus.These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities.

The clinical construct of mild cognitive impairment (MCI) identifies a syndrome of cognitive deficit without dementia, whose fate is unpredictable without an effort to establish the underlying cause. MCI is the natural “reservoir” of subsequent dementing illnesses, but it can be provoked by a variety of psychiatric and systemic diseases as well as by drugs, alcohol, and substance abuse. In this context, morphological and, especially, functional neuroimaging by means of multitracer SPECT and PET provide clue information on the underlying pathological process. Both MRI and SPECT/PET have been included as biomarkers in the revised criteria for the diagnosis of Alzheimer’s disease before dementia; similarly, dopamine transporter SPECT and FDG-PET are supportive features for the diagnosis of cognitive deficit due to diffuse Lewy-body disease or to frontotemporal lobe degeneration, respectively. The advent of amyloid imaging with PET radiopharmaceuticals has paved the way to the noninvasive brain biopsy for beta amyloid and can detect amyloidosis in otherwise healthy individuals. In the advanced memory clinics, appropriate use of neuroimaging is nowadays the cornerstone of correct diagnosis of cognitive disorders. New developments include high-field MRI equipment, new fluorinated PET radiopharmaceuticals for amyloid detection and receptor studies, and the upcoming tool of MRI-PET.

We evaluated the brain metabolic correlates of main indexes of a widely used word list learning test, the Rey Auditory Verbal Memory Test (RAVLT), in a group of elderly subjects with memory complaints. Fifty-four subjects (age: 72.02 ± 7.45; Mini-Mental State Examination (MMSE) score: 28.9 ± 1.24) presenting at a memory clinic complaining of memory deficit, but not demented, and thirty controls (age: 71.87 ± 7.08; MMSE score: 29.1 ± 1.1) were included. Subjects with memory complaints included both patients with (amnestic mild cognitive impairment, aMCI) and without (subjective memory complaints, SMC) impairment on memory tests. All subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), analyzed with statistical parametric. Patients with aMCI but not those with SMC showed the expected posterior cingulate-precuneus and parietal hypometabolism as compared to controls. Correlation was determined for between four indexes of the RAVLT and brain metabolism. The results show a significant correlation between the delayed recall score and metabolism in posterior cingulate gyrus of both hemispheres and in left precuneus, as well as between a score of long-term percent retention and metabolism in left posterior cingulate gyrus, precuneus, and orbitofrontal areas. These correlations survived correction for age, education, and MMSE score. No correlation was found between immediate or total recall scores and glucose metabolism. These data show the relevant role of posterior cingulate-precuneus and orbitofrontal cortices in retention and retrieval of de-contextualized verbal memory material in a group of elderly subjects with memory complaints and shed light on the topography of synaptic dysfunction in these subjects, overlapping that found in the earliest stages of Alzheimer-type neurodegeneration.

Background Robust, extensible and distributed databases integrating clinical, imaging and molecular data represent a substantial challenge for modern neuroscience. It is even more difficult to provide extensible software environments able to effectively target the rapidly changing data requirements and structures of research experiments. There is an increasing request from the neuroscience community for software tools addressing technical challenges about: (i) supporting researchers in the medical field to carry out data analysis using integrated bioinformatics services and tools; (ii) handling multimodal/multiscale data and metadata, enabling the injection of several different data types according to structured schemas; (iii) providing high extensibility, in order to address different requirements deriving from a large variety of applications simply through a user runtime configuration. Methods A dynamically extensible data structure supporting collaborative multidisciplinary research projects in neuroscience has been defined and implemented. We have considered extensibility issues from two different points of view. First, the improvement of data flexibility has been taken into account. This has been done through the development of a methodology for the dynamic creation and use of data types and related metadata, based on the definition of “meta” data model. This way, users are not constrainted to a set of predefined data and the model can be easily extensible and applicable to different contexts. Second, users have been enabled to easily customize and extend the experimental procedures in order to track each step of acquisition or analysis. This has been achieved through a process-event data structure, a multipurpose taxonomic schema composed by two generic main objects: events and processes. Then, a repository has been built based on such data model and structure, and deployed on distributed resources thanks to a Grid-based approach. Finally, data integration aspects have been addressed by providing the repository application with an efficient dynamic interface designed to enable the user to both easily query the data depending on defined datatypes and view all the data of every patient in an integrated and simple way. Results The results of our work have been twofold. First, a dynamically extensible data model has been implemented and tested based on a “meta” data-model enabling users to define their own data types independently from the application context. This data model has allowed users to dynamically include additional data types without the need of rebuilding the underlying database. Then a complex process-event data structure has been built, based on this data model, describing patient-centered diagnostic processes and merging information from data and metadata. Second, a repository implementing such a data structure has been deployed on a distributed Data Grid in order to provide scalability both in terms of data input and data storage and to exploit distributed data and computational approaches in order to share resources more efficiently. Moreover, data managing has been made possible through a friendly web interface. The driving principle of not being forced to preconfigured data types has been satisfied. It is up to users to dynamically configure the data model for the given experiment or data acquisition program, thus making it potentially suitable for customized applications. Conclusions Based on such repository, data managing has been made possible through a friendly web interface. The driving principle of not being forced to preconfigured data types has been satisfied. It is up to users to dynamically configure the data model for the given experiment or data acquisition program, thus making it potentially suitable for customized applications.

Cross-sectional imaging is being increasingly proposed as a suitable tool to characterize carotid plaques. The aim of this work was to correlate the Doppler velocity parameters with the cross-sectional percent stenosis (CPoS) of internal carotid artery (ICA) and to identify the cutoff values of these parameters in five progressive classes of stenosis area severity (ie, 40%-49%, 50%-59%, 60%-69%, 70%-79%, 80%-90%).High-quality scans from 90 patients (mean age, 74 ± 9 years) with 43%-90% ICA stenosis were analyzed. ICA peak-systolic (PSV) and end-diastolic (EDV) velocities were measured at maximum stenosis level. Total ICA area and residual lumen (RL) were measured to derive the CPoS. A simple physical model described by the equation Velocity = Flow rate/Area was considered. Effectively, the CPoS is expected to negatively correlate with the inverse of velocity parameters, assuming flow rate to be constant. Multiple stepwise regression analyses were used to investigate the relationships between velocity and echographic measures.With CPoS as the dependent variable, the first significant regressor was the inverse ICA-EDV (r(2) = 0.64; P.0001) followed by inverse ICA-PSV (r(2) = 0.43; P.0001). ICA-EDV mean values throughout five progressive classes of stenosis were: 28 cm/second for 40%-49% stenosis, 35 cm/second for 50%-59%, 43 cm/second for 60%-69%, 69 cm/second for 70%-79%. and 103 cm/second for 80%-90%. ICA-PSV mean values were: 97 cm/second for 40%-49%, 110 cm/second for 50%-59%, 136 cm/second for 60%-69%, 224 cm/second for 70%-79%, and 286 cm/second for 80%-90%.ICA-EDV is the parameter that better correlates with CPoS. Nevertheless, ICA-PSV maintained a highly significant correlation with CPoS. Moreover, the categorization of Doppler parameters in five progressive classes of severity of stenosis could provide physicians with an easily accessible tool in clinical practice, complementary to the morphological evaluation of cross-sectional stenosis.

This study describes late-onset Alzheimer's disease (LOAD) in the mild cognitive impairment (MCI) stage, debuting with seizures in a 72 year-old woman. Prodromal AD was consistently diagnosed with four among amyloidosis and neurodegeneration biomarkers about 1 year after onset of seizures. Genetic assessment demonstrated apolipoprotein E ε2/ε3 genotype and three intronic single nucleotide substitutions, two in presenilin 1 and one in amyloid-β protein precursor genes. This case of seizures at onset of LOAD with severe signs of brain amyloidosis and neurodegeneration but with just MCI leads to a re-appraisal of the intriguing relationship between AD pathology and neuron excitability in humans.

Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated.Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p0.005 at peak level and p0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side.Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH.These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.

Quantitative analysis of EEG during wakefulness in AD/MCI patients shows a slowing of EEG rhytms, in terms of increase of delta activity and decrease of alpha activity. Some studies show differences in AD/MCI patients even in EEG sleep: an increase in stage 1, number and length of intra-night awakenings, a decrease of Slow Wave Sleep (SWS) and REM sleep. Given the strong relation (bidirectional) between EEG sleep and wakefullness rhythms, the objective of the study is to assess EEG topography during sleep (REM and NREM) and wakefulness, and to assess relationship between sleep EEG modifications and subsequent variations in wakefulness EEG. 8 patients AD, 13 MCI and 9 elderly healthy people performed one-night sleep PSG recordings (19 cortical electrods, EOG, EMG) and wakefulness EEG recordings (5 min with eyes open and 5 min with eyes closed). Analyses of EEG topography of wakefulness, REM and NREM sleep suggest significant differences between MCI groups vs. controls within the alpha band, in terms of lower EEG activity within this frequency range in patients in occipital and temporal derivations compared to controls. Although preliminary, data of EEG topography seems showing the same functional variations both in sleep and wakefulness. Hence, the observed slowing may be an electrophysiological evidence of neurodegenerative processes at a cortical level.

Subtle cognitive impairment can be detected in early Parkinson's disease (PD). In a consecutive series of de novo, drug-naive PD patients, we applied stepwise regression analysis to assess which clinical, neuropsychological, and functional neuroimaging (dopamine transporter [DAT] and perfusion single photon emission computed tomography [SPECT]) characteristics at baseline was predictive of cognitive decline during an average follow-up time of about 4 years. Decline both in executive (R2 = 0.54; p = 0.0001) and visuospatial (R2 = 0.56; p = 0.0001) functions was predicted by the couple of Unified Parkinson's Disease Rating Scale (UPDRS)-III score and caudate dopamine transporter (DAT) uptake in the less affected hemisphere (LAH). Verbal memory and language decline was predicted instead by caudate DAT uptake and brain perfusion in a posterior parieto-temporal area of the less affected hemisphere (R2 = 0.42; p = 0.0005). No significant effect was shown for age, baseline neuropsychological scores, and levodopa equivalent dose at follow-up. The combined use of clinical structured examination and brain functional assessment by means of dual single photon emission computed tomography imaging appears as a powerful approach to predict cognitive decline in de novo PD patients.