Conflicting results are available on the association of prothrombotic genetic abnormalities with ... more Conflicting results are available on the association of prothrombotic genetic abnormalities with patent foramen ovale (PFO)-related cerebral ischaemia. We comprehensively sought and identified studies of the association of both the factor V Leiden (FV(G1691A) mutation) and the prothrombin mutation (PT(G20210A) mutation) with PFO-related cerebral ischaemia and did meta-analyses to assess the evidence for such a relation. We analysed data from six eligible studies in 856 cases and 1,001 control subjects. Additional unpublished data from a new series including 463 subjects were also entered into the analysis. The PT(G20210A) variant was significantly associated with PFO-related stroke in comparison with both control subjects (odds ratio [OR] 3.85; 95% confidence interval [CI] 2.22 to 6.66) and non-PFO-associated stroke patients (OR 2.31; 95% CI 1.20 to 4.43), whereas a trend toward an association was observed for the FV(G1691A) mutation (OR 1.18; 95% CI 0.73 to 1.90, compared to control subjects; OR 1.14; 95% CI 0.62 to 2.09, compared to non-PFO-associated stroke patients). The status of carrier of either the FV(G1691A) mutation or the PT(G20210A) variant was associated with a risk for stroke of 1.98 (95% CI 1.38 to 2.83) and 1.62 (95% CI 1.03 to 2.57), as compared to control subjects and non-PFO-associated stroke patients, respectively. Addition of common prothrombotic genetic variants to standard initial screening may contribute to stratifying PFO-associated stroke patients at different risk of ischaemic events and targeting secondary prevention strategies.
ObjectiveThis study, by taking a holistic approach, investigates the relationships between taste,... more ObjectiveThis study, by taking a holistic approach, investigates the relationships between taste, smell sensitivity and food preference with prognostic (endogenous and health) factors including age, gender, genetic taste markers, body mass, cigarette smoking, and number of drugs used.DesignCross sectional study.SettingNorthern Italy.Participants203 healthy subjects (160 women/43 men; mean age: 58.2±19.8 years) were examined.MeasurementsIndividual taste sensitivity was determined by saccharose, sodium chloride, acetic acid and caffeine solutions and by 6-n-propylthiouracil (PROP) responsiveness test. Olfactory sensitivity has been assessed by «Sniffin’ Sticks». Four tag Single nucleotide polymorphisms (SNPs) in regions of interest were genotyped. Factor analysis and multivariate regression were performed for scaling food preferences and screening prognostic factors, respectively.ResultsIncreasing age is associated with decreased responsiveness to NaCl (P=0.001), sweet solutions (P=0.044), and smell perception (P<0.001). Concerning the food preferences, elderly like the “vegetables” and “fruits” but dislike “spicy” more than younger. Regarding number of drugs taken, there is a significant negative effect on smell perception (P<0.001). In addition, drugs reduce both the “vegetables foods” score (P=0.002) and the “milk-product foods” score (P=0.027). With respect to Body Mass Index (BMI), only a significant effect was shown, on sweet perception (P=0.006). Variation in taste receptor genes can give rise to differential perception of sweet, acid and bitter tastes. No effect of gender and smoking was observed.ConclusionsOur study suggested that age, genetic markers, BMI and drugs use are the factors which affect taste and smell perception and food preferences.
ObjectiveEpidemiological data to characterize the individual risk profile of patients with sponta... more ObjectiveEpidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent.Methods and ResultsIn the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non‐CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke‐free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke‐free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37–1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74–3.34), without aura (OR = 2.67, 95% CI = 2.15–3.32), and family history of vascular disease in first‐degree relatives (OR = 1.69, 95% CI = 1.39–2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47–0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62–0.91), and obese (OR = 0.41, 95% CI = 0.31–0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47–2.22) in comparison with patients with non‐CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti‐migraine preventive medications, especially beta‐blockers, compared with the other groups.InterpretationThe risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta‐blockers. ANN NEUROL 2023;94:585–595
ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, a... more ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).MethodsWe performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5‐fold cross‐validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder.ResultsA total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86–0.92), high recall (0.93–0.98), and high F1 scores (0.89–0.95) in differentiating each neurodegenerative disorder.InterpretationTMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394–404
Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor ... more Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for 2 weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5...
ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, a... more ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).MethodsWe performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5‐fold cross‐validation. The primary outcome measures were the cla...
SummaryFactors predicting family history (FH) of premature arterial thrombosis in young patients ... more SummaryFactors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18–45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] > 45 years in proband’s first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n= 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21–3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21–6.06). Smoking (OR, 2.48; 95 % CI, 1.20–5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31–10.10), and the A20...
In this paper , Principal Component Analysis (PCA) is formulated within a likelihood framework, b... more In this paper , Principal Component Analysis (PCA) is formulated within a likelihood framework, based on a specific form of Gaussian model. We suggest how the principal axes of observed data vectors may be determined through maximum-likelihood estimation of parameters in a latent variable model closely related to a Factor Analysis and Error-in-Variables Models. We consider the properties of the associated likelihood function and discuss the advantages conveyed by the definition of a probability density function for PCA. The numeric/graphical quantities of the usual output now represent the maximum likelihood estimates of the parameters of a probabilistic model, rather than approximations of an algebraic-geometric algorithm. The use of PCA as method of analysis communicated by the interpretation of the principal components: we determine the subdivision a posteriori predictors of redundant variables. We investigate the proposed model in a case-control study of cardiovascular disease.
Conflicting results are available on the association of prothrombotic genetic abnormalities with ... more Conflicting results are available on the association of prothrombotic genetic abnormalities with patent foramen ovale (PFO)-related cerebral ischaemia. We comprehensively sought and identified studies of the association of both the factor V Leiden (FV(G1691A) mutation) and the prothrombin mutation (PT(G20210A) mutation) with PFO-related cerebral ischaemia and did meta-analyses to assess the evidence for such a relation. We analysed data from six eligible studies in 856 cases and 1,001 control subjects. Additional unpublished data from a new series including 463 subjects were also entered into the analysis. The PT(G20210A) variant was significantly associated with PFO-related stroke in comparison with both control subjects (odds ratio [OR] 3.85; 95% confidence interval [CI] 2.22 to 6.66) and non-PFO-associated stroke patients (OR 2.31; 95% CI 1.20 to 4.43), whereas a trend toward an association was observed for the FV(G1691A) mutation (OR 1.18; 95% CI 0.73 to 1.90, compared to control subjects; OR 1.14; 95% CI 0.62 to 2.09, compared to non-PFO-associated stroke patients). The status of carrier of either the FV(G1691A) mutation or the PT(G20210A) variant was associated with a risk for stroke of 1.98 (95% CI 1.38 to 2.83) and 1.62 (95% CI 1.03 to 2.57), as compared to control subjects and non-PFO-associated stroke patients, respectively. Addition of common prothrombotic genetic variants to standard initial screening may contribute to stratifying PFO-associated stroke patients at different risk of ischaemic events and targeting secondary prevention strategies.
ObjectiveThis study, by taking a holistic approach, investigates the relationships between taste,... more ObjectiveThis study, by taking a holistic approach, investigates the relationships between taste, smell sensitivity and food preference with prognostic (endogenous and health) factors including age, gender, genetic taste markers, body mass, cigarette smoking, and number of drugs used.DesignCross sectional study.SettingNorthern Italy.Participants203 healthy subjects (160 women/43 men; mean age: 58.2±19.8 years) were examined.MeasurementsIndividual taste sensitivity was determined by saccharose, sodium chloride, acetic acid and caffeine solutions and by 6-n-propylthiouracil (PROP) responsiveness test. Olfactory sensitivity has been assessed by «Sniffin’ Sticks». Four tag Single nucleotide polymorphisms (SNPs) in regions of interest were genotyped. Factor analysis and multivariate regression were performed for scaling food preferences and screening prognostic factors, respectively.ResultsIncreasing age is associated with decreased responsiveness to NaCl (P=0.001), sweet solutions (P=0.044), and smell perception (P<0.001). Concerning the food preferences, elderly like the “vegetables” and “fruits” but dislike “spicy” more than younger. Regarding number of drugs taken, there is a significant negative effect on smell perception (P<0.001). In addition, drugs reduce both the “vegetables foods” score (P=0.002) and the “milk-product foods” score (P=0.027). With respect to Body Mass Index (BMI), only a significant effect was shown, on sweet perception (P=0.006). Variation in taste receptor genes can give rise to differential perception of sweet, acid and bitter tastes. No effect of gender and smoking was observed.ConclusionsOur study suggested that age, genetic markers, BMI and drugs use are the factors which affect taste and smell perception and food preferences.
ObjectiveEpidemiological data to characterize the individual risk profile of patients with sponta... more ObjectiveEpidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent.Methods and ResultsIn the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non‐CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke‐free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke‐free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37–1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74–3.34), without aura (OR = 2.67, 95% CI = 2.15–3.32), and family history of vascular disease in first‐degree relatives (OR = 1.69, 95% CI = 1.39–2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47–0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62–0.91), and obese (OR = 0.41, 95% CI = 0.31–0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47–2.22) in comparison with patients with non‐CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti‐migraine preventive medications, especially beta‐blockers, compared with the other groups.InterpretationThe risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta‐blockers. ANN NEUROL 2023;94:585–595
ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, a... more ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).MethodsWe performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5‐fold cross‐validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder.ResultsA total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86–0.92), high recall (0.93–0.98), and high F1 scores (0.89–0.95) in differentiating each neurodegenerative disorder.InterpretationTMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394–404
Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor ... more Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for 2 weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5...
ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, a... more ObjectiveTranscranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).MethodsWe performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5‐fold cross‐validation. The primary outcome measures were the cla...
SummaryFactors predicting family history (FH) of premature arterial thrombosis in young patients ... more SummaryFactors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18–45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] > 45 years in proband’s first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n= 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21–3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21–6.06). Smoking (OR, 2.48; 95 % CI, 1.20–5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31–10.10), and the A20...
In this paper , Principal Component Analysis (PCA) is formulated within a likelihood framework, b... more In this paper , Principal Component Analysis (PCA) is formulated within a likelihood framework, based on a specific form of Gaussian model. We suggest how the principal axes of observed data vectors may be determined through maximum-likelihood estimation of parameters in a latent variable model closely related to a Factor Analysis and Error-in-Variables Models. We consider the properties of the associated likelihood function and discuss the advantages conveyed by the definition of a probability density function for PCA. The numeric/graphical quantities of the usual output now represent the maximum likelihood estimates of the parameters of a probabilistic model, rather than approximations of an algebraic-geometric algorithm. The use of PCA as method of analysis communicated by the interpretation of the principal components: we determine the subdivision a posteriori predictors of redundant variables. We investigate the proposed model in a case-control study of cardiovascular disease.
Uploads