Patterns of Brain Structural Changes in First-Contact, Antipsychotic Drug-Naïve Patients with Schizophrenia

BACKGROUND AND PURPOSE: Previous studies have suggested that structural changes do occur in the brain of patients with schizophrenia compared with healthy control participants. However, findings from such studies are inconclusive, probably because of the different methodologic approaches, the clinical heterogeneity of patient samples, and also the fact that patients enrolled were treated with antipsychotic drugs. The aim of this study was to investigate brain GM volumes and intrinsic structural WM changes in first-contact, antipsychotic drug-naive patients with schizophrenia. MATERIALS AND METHODS: A total of 43 first-contact, drug-naive, patients with schizophrenia and 17 age-matched control participants were studied. All participants underwent T1-weighted MR imaging and DTI scans. Voxel-based morphometry and tract-based spatial statistics were used to compare GM volumes and WM DTI metrics between groups. MR imaging measures were correlated with the duration of the untreated psychosis and the clinical positive and negative symptoms. RESULTS: Compared with control participants, patients with schizophrenia showed smaller volumes of the temporal, parietal, and occipital GM, and a pattern of decreased mean diffusivity and increased fractional anisotropy in the brain stem and cerebellum bilaterally, interhemispheric and cortico-cortical connections bilaterally, and right anterior and posterior limb of the internal capsule. In patients, decreased mean diffusivity and increased fractional anisotropy in several brain regions were related to a longer duration of the untreated psychosis and the severity of positive symptoms. CONCLUSIONS: First-contact, drug-naive, patients with schizophrenia present with volumetric and DTI changes, which correlated with their clinical features. This study increases our knowledge on the neural networks involved in the pathophysiologic mechanisms of schizophrenia

Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect.

BACKGROUND AND PURPOSE: The objective was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis and in the migraine-ischemic stroke pathway. METHODS: A first genotype-migraine association study was conducted on 100 patients with migraine with aura (MA), 106 with migraine without aura (MO), and 105 subjects without migraine, which provided evidence in favor of association of the TT677 MTHFR genotype with increased risk of MA compared with both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the genotype-migraine-stroke pathway were fitted on a group of 106 patients with spontaneous cervical artery dissection, 227 young patients whose ischemic stroke was unrelated to a spontaneous cervical artery dissection (noncervical artery dissection), and 187 control subjects, and a genotype-migraine partial mediation model was selected. RESULTS: Both migraine and the TT genotype were more strongly associated to the subgroup of patients with spontaneous cervical artery dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to 9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI, 1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared with controls. CONCLUSIONS: Migraine may act as mediator in the methylenetetrahydrofolate reductase-ischemic stroke pathway with a more prominent effect in the subgroup of patients with spontaneous artery dissection

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. Results: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. Conclusions: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations

Neuro-environmental interactions: a time sensitive matter

Introduction: The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI). Methods: We implemented an interpretable XGBoost-shapley additive explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages, 13-25 years) enrolled in the public health impact of metals exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, copper, nickel, and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood, and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex. Results: Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated (p < 0.001, r = 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics. Discussion: Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

IntroductionAdolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents. MethodsIn 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age. ResultsWe observed significant negative associations between the metal mixture and GE and LE [beta GE = -0.076, 95% CI (-0.122, -0.031); beta LE= -0.051, 95% CI (-0.095, -0.006)]. Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE. DiscussionOur results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal

Italian hospitals on the web: a cross-sectional analysis of official websites

<p>Abstract</p> <p>Background</p> <p>Although the use of the Internet for health purposes has increased steadily in the last decade, only a few studies have explored the information provided by the websites of health institutions and no studies on the on-line activities of Italian hospitals have been performed to date. The aim of this study was to explore the characteristics of the contents and the user-orientation of Italian hospital websites.</p> <p>Methods</p> <p>The cross-sectional analysis considered all the Italian hospitals with a working website between December 2008 and February 2009. The websites were coded using an <it>ad hoc </it>Codebook, comprising eighty-nine items divided into five sections: technical characteristics, hospital information and facilities, medical services, interactive on-line services and external activities. We calculated a website evaluation score, on the basis of the items satisfied, to compare private (PrHs) and public hospitals, the latter divided into ones with their own website (PubHs-1) and ones with a section on the website of their Local Health Authority (PubHs-2). Lastly, a descriptive analysis of each item was carried out.</p> <p>Results</p> <p>Out of the 1265 hospitals in Italy, we found that 419 of the 652 public hospitals (64.3%) and 344 of the 613 PrHs (56.1%) had a working website (p = 0.01). The mean website evaluation score was 41.9 for PubHs-1, 21.2 for PubHs-2 and 30.8 for PrHs (p < 0.001).</p> <p>Only 5 hospitals out of 763 (< 1%) provided specific clinical performance indicators, such as the nosocomial infection rate or the surgical mortality rates. Regarding interactive on-line services, although nearly 80% of both public and private hospitals enabled users to communicate on-line, less than 18% allowed the reservation of medical services, and only 8 websites (1%) provided a health-care forum.</p> <p>Conclusions</p> <p>A high percentage of hospitals did not provide an official website and the majority of the websites found had several limitations. Very few hospitals provided information to increase the credibility of the hospital and user confidence in the institution. This study suggests that Italian hospital websites are more a source of information on admissions and services than a means of communication between user and hospital.</p

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998–2012

Background: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. Methods: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. Results: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12–1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42–1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon–rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. Conclusions: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS

Combined intravenous and endovascular treatment versus primary mechanical thrombectomy. The Italian Registry of Endovascular Treatment in Acute Stroke

Background: Whether mechanical thrombectomy alone may achieve better or at least equal clinical outcome than mechanical thrombectomy combined with intravenous thrombolysis is a matter of debate. Methods: From the Italian Registry of Endovascular Stroke Treatment, we extracted all cases treated with intravenous thrombolysis followed by mechanical thrombectomy or with primary mechanical thrombectomy for anterior circulation stroke due to proximal vessel occlusion. We included only patients who would have qualified for intravenous thrombolysis. We compared outcomes of the two groups by using multivariate regression analysis and propensity score method. Results: We included 1148 patients, treated with combined intravenous thrombolysis and mechanical thrombectomy therapy (n = 635; 55.3%), or with mechanical thrombectomy alone (n = 513; 44.7%). Demographic and baseline clinical characteristics did not differ between the two groups, except for a shorter onset to groin puncture time (p &lt; 0.05) in the mechanical thrombectomy group. A shift in the 90-day modified Rankin Scale distributions toward a better outcome was found in favor of the combined treatment (adjusted common odds ratio = 1.3; 95% confidence interval: 1.04–1.66). Multivariate analyses on binary outcome show that subjects who underwent combined treatment had higher probability to survive with modified Rankin Scale 0–3 (odds ratio = 1.42; 95% confidence interval: 1.04–1.95) and lower case fatality rate (odds ratio = 0.6; 95% confidence interval: 0.44–0.9). Hemorrhagic transformation did not differ between the two groups. Conclusion: These data seem to indicate that combined intravenous thrombolysis and mechanical thrombectomy could be associated with lower probability of death or severe dependency after three months from stroke due to large vessel occlusion, supporting the current guidelines of treating eligible patients with intravenous thrombolysis before mechanical thrombectomy

History of migraine and volume of brain infarcts: The italian project on stroke at young age (IPSYS)

BACKGROUND AND PURPOSE: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSION: s These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine