Towards personalized diagnosis of Glioblastoma in Fluid-attenuated inversion recovery (FLAIR) by topological interpretable machine learning

Glioblastoma multiforme (GBM) is a fast-growing and highly invasive brain tumour, it tends to occur in adults between the ages of 45 and 70 and it accounts for 52 percent of all primary brain tumours. Usually, GBMs are detected by magnetic resonance images (MRI). Among MRI, Fluid-attenuated inversion recovery (FLAIR) sequence produces high quality digital tumour representation. Fast detection and segmentation techniques are needed for overcoming subjective medical doctors (MDs) judgment. In the present investigation, we intend to demonstrate by means of numerical experiments that topological features combined with textural features can be enrolled for GBM analysis and morphological characterization on FLAIR. To this extent, we have performed three numerical experiments. In the first experiment, Topological Data Analysis (TDA) of a simplified 2D tumour growth mathematical model had allowed to understand the bio-chemical conditions that facilitate tumour growth: the higher the concentration of chemical nutrients the more virulent the process. In the second experiment topological data analysis was used for evaluating GBM temporal progression on FLAIR recorded within 90 days following treatment (e.g., chemo-radiation therapy - CRT) completion and at progression. The experiment had confirmed that persistent entropy is a viable statistics for monitoring GBM evolution during the follow-up period. In the third experiment we had developed a novel methodology based on topological and textural features and automatic interpretable machine learning for automatic GBM classification on FLAIR. The algorithm reached a classification accuracy up to the 97%.Comment: 22 pages; 16 figure

Sleep actigraphic patterns and cognitive status

none9noWe performed an actigraphic assessment of sleep characteristics in healthy subjects and patients with cognitive impairment. Thirty subjects were included and classified into controls (10 subjects), mild cognitive impairment (10 patients) and mild-to-moderate Alzheimer's disease (10 patients). Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Participants had a 7-day actigraphic record. Sleep parameters collected were time in bed, total sleep time, sleep efficiency, sleep latency, wakefulness after sleep onset, number of awakenings, and mean motor activity. Significant differences between mild cognitive impairment and controls patients were found for sleep latency (p = 0.05); Alzheimer's disease patients had significantly worse scores for Pittsburgh Sleep Quality Index (p = 0.01), time in bed (p = 0.001), total sleep time (p = 0.04), sleep latency, sleep efficiency, motor activity (p = 0.0001) and wakefulness after sleep onset (p = 0.001) compared to controls. When comparing Alzheimer's disease and mild cognitive impairment, differences were significant for sleep latency (p = 0.01), wakefulness after sleep onset (p = 0.004), sleep efficiency, number of awakenings and motor activity (p = 0.0001). In addition to showing a high prevalence of sleep alterations in subjects with cognitive impairment, our data suggest that they are evident from the earliest stages of cognitive decline. Further studies are needed to assess whether early correction of sleep alterations can positively influence the evolution of cognitive impairment. The opportunity to provide clinically meaningful information with a simple assessment of sleep characteristics based on actigraphy suggests that wider use of the approach in patients with cognitive decline should be considered.openBuratti, Laura; Camilletti, Roberta; Pulcini, Alessandra; Rocchi, Chiara; Viticchi, Giovanna; Falsetti, Lorenzo; Baldinelli, Sara; Fiori, Chiara; Silvestrini, MauroBuratti, Laura; Camilletti, Roberta; Pulcini, Alessandra; Rocchi, Chiara; Viticchi, Giovanna; Falsetti, Lorenzo; Baldinelli, Sara; Fiori, Chiara; Silvestrini, Maur

Ipsilateral and contralateral carotid stenosis contribute to the outcome of reperfusion treatment for ischemic stroke

IntroductionIpsilateral and contralateral carotid stenosis (ICS, CCS) influence acute ischemic stroke (AIS) severity and prognosis. Few data are available about their impact on reperfusion therapies efficacy. Aim of this study was to evaluate the impact of ICS and CCS on the effect of intravenous thrombolysis (IT), mechanical thrombectomy (MT) or both and of antiplatelet therapy (AT).MethodsWe enrolled all the consecutive patients admitted for AIS to our stroke unit and submitted to IT, MT, IT+MT, or AT. We established the presence of a significant ICS or CCS (≥70%) by ultrasound examination or brain angio-CT, or MRI. Clinical and instrumental information were collected; delta National Institutes of Health Stroke Scale (NIHSS) from pre-treatment to patients' discharge was employed as the main outcome measure.ResultsIn total, 460 subjects were enrolled, 86 with ICS and 38 with CCS. We observed a significant linear trend of delta (NIHSS) between carotid stenosis categories for patients undergoing IT (p = 0.011), MT (p = 0.046), and MT+IT (p = 0.040), but no significant trend among subjects receiving no reperfusion treatments was observed (p = 0.174).DiscussionAccording to our findings, ICS and CCS negatively influence AIS patients' outcome treated by interventional therapies. ICS might exert an unfavorable effect both by cerebral hypoperfusion and by continuous microembolization toward ischemic area, while CCS is probable involved in reducing the collateral circles effectiveness. The importance of early carotid stenosis detection and treatment should then be reevaluated not only to manage the prevention approaches but also to obtain insights about post-stroke treatment strategies efficacy

Risk prediction of clinical adverse outcomes with machine learning in a cohort of critically ill patients with atrial fibrillation

Critically ill patients affected by atrial fibrillation are at high risk of adverse events: however, the actual risk stratification models for haemorrhagic and thrombotic events are not validated in a critical care setting. With this paper we aimed to identify, adopting topological data analysis, the risk factors for therapeutic failure (in-hospital death or intensive care unit transfer), the in-hospital occurrence of stroke/TIA and major bleeding in a cohort of critically ill patients with pre-existing atrial fibrillation admitted to a stepdown unit; to engineer newer prediction models based on machine learning in the same cohort. We selected all medical patients admitted for critical illness and a history of pre-existing atrial fibrillation in the timeframe 01/01/2002-03/08/2007. All data regarding patients' medical history, comorbidities, drugs adopted, vital parameters and outcomes (therapeutic failure, stroke/TIA and major bleeding) were acquired from electronic medical records. Risk factors for each outcome were analyzed adopting topological data analysis. Machine learning was used to generate three different predictive models. We were able to identify specific risk factors and to engineer dedicated clinical prediction models for therapeutic failure (AUC: 0.974, 95%CI: 0.934-0.975), stroke/TIA (AUC: 0.931, 95%CI: 0.896-0.940; Brier score: 0.13) and major bleeding (AUC: 0.930:0.911-0.939; Brier score: 0.09) in critically-ill patients, which were able to predict accurately their respective clinical outcomes. Topological data analysis and machine learning techniques represent a concrete viewpoint for the physician to predict the risk at the patients' level, aiding the selection of the best therapeutic strategy in critically ill patients affected by pre-existing atrial fibrillation

Stroke territory and atherosclerosis in ischemic stroke patients with a history of migraine with aura

IntroductionThe mechanisms subtending the increased stroke risk in migraine with aura (MA) are not fully understood. Our study aims to evaluate if the clinical profile in stroke patients with MA differentiates from those without MA.MethodsWe retrieved the prospective registered electronic clinical dossiers of adult patients younger than 60 years with acute ischemic stroke admitted in four hospitals between January 2016 and June 2022. Patients were classified by the history of MA (MA+ and MA–).ResultsWe identified 851 stroke patients (59 MA+, 6.9%). Compared to MA−, MA+ patients were characterized by younger age (44.0 ± 10.6 vs 50.1 ± 8.2 years), female sex (59.3% vs 29.0%), and affected by cryptogenic (OR 2.594 95% CI 1.483–4.537), and cerebellar stroke (OR 3.218 95% CI 1.657–6.250; p ≤ 0.001 for all comparisons). After adjusting for age and sex, MA+ patients presented less frequently hypertension (OR 0.349 95% CI 0.167–0.470; p=0.005) and dyslipidemia (OR 0.523 95% CI 0.280–0.974; p = 0.041). After adjusting also for risk factors, the MA+ group had less frequently symptomatic large vessel stenosis (OR 0.126 95% CI 0.017–0,924; p = 0.042) and clinical atherosclerosis (OR 0.103 95% CI 0.014–0.761; p = 0.026), while intima–media thickness did not differ (p = 0.395).DiscussionCryptogenic and cerebellar stroke and fewer vascular risk factors and clinical atherosclerosis seem to characterize stroke patients with MA

Can Framingham Risk Score predict cognitive decline progression in Alzheimer\u2019s Disease ?

Background and Aims: The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis emerged. Aim of the study was to investigate, in a population of Alzheimers Disease (AD) patients, the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration. Patients and Methods: 284 consecutive AD patients were enrolled. For each patient, FCRP score was calculated. APOE alleles were evaluated in order to assess genetic predisposition do develop a more aggressive cognitive deterioration. We performed a one-year-follow-up in order to quantify the cognitive decline by the Clinical Dementia Rating score changes. Results: FCPR score predicted cognitive deterioration with an AUC of 0.63 (95%CI: 0.57-0.69; p<0.0001). In the sub-population of patients with a genetic increased predisposition to develop cognitive deterioration, and with an advanced vascular impairment, FRCP predictive value significantly increased with an AUC of 0.77 (95%CI: 0.52-0.93; p<0.05). Our findings show that FCRP, a cluster of vascular risk factors, can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors

Ditans: a new prospective for the therapy of migraine attack?

Migraine attack is characterized by disabling pain and associated symptoms. Triptans represent the "gold standard" therapy, but cardiac subjects have significant limitations for this approach. New drug families are under consideration to expand therapeutic offerings, especially in the presence of contraindications or for non-responsive patients. This review aimed to analyze studies related to the category of "ditans," with a focus on lasmiditan, which is available for human use

Cerebral Hemodynamic and Cognitive Performance in Bilateral Asymptomatic Carotid Stenosis

Background: Preliminary studies have reported cognitive dysfunction in unilateral asymptomatic carotid stenosis (ACS). Impaired cerebral hemodynamic status measured by cerebrovascular reactivity has been associated with cognitive dysfunction in unilateral ACS. Objectives: (1) To evaluate cognitive performance in bilateral ACS compared to unilateral ACS and healthy subjects and (2) to explore the relationship between cognitive performance and cerebral hemodynamic status in bilateral ACS. Method: Asymptomatic patients with ultrasound evidence of bilateral or unilateral ACS (60%-99% diameter reduction) were prospectively collected. Healthy subjects (HS) comparable for demographics and vascular risk profile served as controls. A neuropsychological investigation included phonemic and categorical Verbal Fluency (VF) tests to explore the left hemisphere and Colored Progressive Matrices (CPM), and Complex Figure Test Copy (CFTC) tests to explore the right hemisphere. Cerebrovascular reactivity (CVR) to hypercapnia using the transcranial Doppler (TCD) based breath-holding index (BHI) test was performed in each subject. Impaired CVR was defined as a BHI < 0.69. Generalized linear multivariate and univariate models were employed to evaluate the mean difference on left and right cognitive test abilities in bilateral ACS patients with left and right preserved or impaired CVR. Vascular risk factors, education years, mini-mental status examination (MMSE), and current medications were included as covariates. Results: Three-hundred-thirty-three consecutive subjects were included: 126 bilateral ACS; 73/75 left/ right unilateral ACS; 56 HS; mean age: 70 \ub1 3.78 yrs; males: 65%; education years: 10.3\ub13.7; MMSE score: 26.7\ub11.27. Bilateral and unilateral ACS patients showed significantly lower scores in all cognitive tests compared to HS (p<0.05). In the multivariate analysis, among bilateral ACS an impaired CVR in the right side was associated with a significantly reduced CPM score: from an estimated mean of 32.6 [95% Confidence Interval (CI): 29.8-35.4) to 23.0 (95% CI: 20.2-25.8) and the CFTC score from 34.7 (95% CI: 32.0-37.4) to 26.0 (95% CI: 23.3-28.7). Similarly, an impaired CVR on the left side was associated with a reduced phonemic VF score: 13.5 (95% CI: 11.2-15.8) to 7.5 (95% CI: 5.4-9.7) and categorical VF score from 21.1 (95% CI: 18.1-24.1) to 12.3 (95% CI: 9.5-15.1). All comparisons were p<0.05. Conclusion: Patients with unilateral or bilateral ACS are more likely to suffer cognitive dysfunction compared to healthy controls. Impaired CVR predicts the development of cognitive dysfunction in bilateral ACS. A non-invasive assessment of CVR using the TCD-based BHI test may contribute to a more comprehensive risk stratification in these patients

Cerebral haemodynamics and cognitive deterioration in bilateral asymptomatic severe carotid stenosis

Background and Purpose: We aimed to evaluate cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. Methods: 159 subjects with bilateral asymptomatic severe internal carotid ar- tery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Ex- amination (MMSE) at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler–based breath-holding index test. As a mea- sure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. Results: The risk of decreasing in MMSE score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bi- laterally abnormal breath-holding index (P<0.0001). Pathological values of intima-media thickness did not influence the risk of MMSE score change. Conclusions: Our findings suggest that patients with asymptomatic bi- lateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dys- function present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments

Cerebral hemodynamics and cognitive performance in bilateral asymptomatic carotid stenosis

Objectives: To evaluate cognitive performance in subjects with bilateral asymptomatic carotid stenosis (B-ACS) compared to subjects with unilateral ACS and to subjects with no carotid stenosis (CS) and to explore the relationship between cognitive performance and cerebral hemodynamics status in B-ACS. Methods: The neuropsychological investigation included phonemic (ph) and categorical (ca) Verbal Fluency (VF) tests for exploring the left brain functions and Colored Progressive Matrices (CPM) and Complex Figure Copy Test (CFCT) for the right brain. Cerebral hemodynamics status was assessed using the transcranial Doppler-based breath-holding index test. Results: A total of 333 subjects were included: 127 B-ACS, 73/77 left/right unilateral ACS, 56 no CS, mean age 70 \uc2\ub1 3.78 years, 65% male. Subjects with B-ACS and subjects with unilateral ACS showed significantly lower scores in all cognitive tests compared to subjects with no CS (p < 0.05). Subjects with B-ACS with left impaired hemodynamics status showed a significantly reduced ph-VF score, from 13.4 (95% confidence interval [CI] 11.2-15.8) to 7.5 (95% CI 5.4-9.7), and a reduced ca-VF score, from 19.7 (95% CI 18.1-24.1) to 10.8 (95% CI 9.5-15.1), compared to subjects with no CS. Similarly, impaired cerebral hemodynamics in the right side was associated with a significantly reduced CPM score, from an estimated mean of 34.2 (95% CI 29.8-35.4) to 24.6 (95% CI 20.2-25.8), and CFCT score from 37.0 (95% CI 32.0-37.4) to 27.1 (95% CI 23.3-28.7). All comparisons were p < 0.05. Conclusion: Subjects with B-ACS and subjects with unilateral ACS are more likely to have cognitive dysfunction compared to subjects with no CS. There appears to be a link between cognitive dysfunction and hemodynamics impairment due to carotid stenosis. Copyright \uc2\ua9 2012 by AAN Enterprises, Inc