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Article ; Online: Sex differences in mild vascular cognitive impairment: A multimodal transcranial magnetic stimulation study.

Cantone, Mariagiovanna / Fisicaro, Francesco / Ferri, Raffaele / Bella, Rita / Pennisi, Giovanni / Lanza, Giuseppe / Pennisi, Manuela

PloS one

2023 Volume 18, Issue 3, Page(s) e0282751

Abstract: Background: Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a ... ...

Abstract	Background: Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking. Methods: Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs). Results: Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden. Conclusions: We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.
MeSH term(s)	Humans ; Female ; Male ; Transcranial Magnetic Stimulation ; Sex Characteristics ; Cognitive Dysfunction ; Anthropometry
Chemical Substances	1-cyclohexyl-3-(2-(4-morpholinyl)ethyl)carbodiimide (15580-20-8)
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0282751
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The supporting (sometimes decisive!) role of transcranial magnetic stimulation in forensic medicine.

Fisicaro, Francesco / Liberto, Aldo / Lanza, Giuseppe / Bella, Rita / Pennisi, Giovanni / Ferri, Raffaele / Terao, Yasuo / Ugawa, Yoshikazu / Pennisi, Manuela

Brain stimulation

2023 Volume 16, Issue 1, Page(s) 111–113

MeSH term(s)	Transcranial Magnetic Stimulation ; Transcranial Direct Current Stimulation ; Forensic Medicine
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Letter
ZDB-ID	2394410-9
ISSN	1876-4754 ; 1935-861X
ISSN (online)	1876-4754
ISSN	1935-861X
DOI	10.1016/j.brs.2023.01.1677
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Article ; Online: Sex differences in mild vascular cognitive impairment

Mariagiovanna Cantone / Francesco Fisicaro / Raffaele Ferri / Rita Bella / Giovanni Pennisi / Giuseppe Lanza / Manuela Pennisi

PLoS ONE, Vol 18, Iss 3, p e

A multimodal transcranial magnetic stimulation study.

2023 Volume 0282751

Abstract: Background Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a ... ...

Abstract	Background Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking. Methods Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs). Results Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden. Conclusions We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Sex-specific reference values for total, central, and peripheral latency of motor evoked potentials from a large cohort.

Cantone, Mariagiovanna / Lanza, Giuseppe / Fisicaro, Francesco / Bella, Rita / Ferri, Raffaele / Pennisi, Giovanni / Waterstraat, Gunnar / Pennisi, Manuela

Frontiers in human neuroscience

2023 Volume 17, Page(s) 1152204

Abstract: Background: Differentiating between physiologic and altered motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) is crucial in clinical practice. Some physical characteristics, such as height and age, introduce sources of ... ...

Abstract	Background: Differentiating between physiologic and altered motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) is crucial in clinical practice. Some physical characteristics, such as height and age, introduce sources of variability unrelated to neural dysfunction. We provided new age- and height-adjusted normal values for cortical latency, central motor conduction time (CMCT), and peripheral motor conduction time (PMCT) from a large cohort of healthy subjects. Methods: Previously reported data from 587 participants were re-analyzed. Nervous system disorders were ruled out by clinical examination and magnetic resonance imaging. MEP latency was determined as stimulus-to-response latency through stimulation with a circular coil over the "hot spot" of the First Dorsal Interosseous and Tibialis Anterior muscles, during mild tonic contraction. CMCT was estimated as the difference between MEP cortical latency and PMCT by radicular magnetic stimulation. Additionally, right-to-left differences were calculated. For each parameter, multiple linear regression models of increasing complexity were fitted using height, age, and sex as regressors. Results: Motor evoked potential cortical latency, PMCT, and CMCT were shown to be age- and height-dependent, although age had only a small effect on CMCT. Relying on Bayesian information criterion for model selection, MEP cortical latency and PMCT were explained best by linear models indicating a positive correlation with both height and age. Also, CMCT to lower limbs positively correlated with height and age. CMCT to upper limbs positively correlated to height, but slightly inversely correlated to age, as supported by non-parametric bootstrap analysis. Males had longer cortical latencies and CMCT to lower limbs, as well as longer PMCT and cortical latencies to upper limbs, even when accounting for differences in body height. Right-to-left-differences were independent of height, age, and sex. Based on the selected regression models, sex-specific reference values were obtained for all TMS-related latencies and inter-side differences, with adjustments for height and age, where warranted. Conclusion: A significant relationship was observed between height and age and all MEP latency values, in both upper and lower limbs. These set of reference values facilitate the evaluation of MEPs in clinical studies and research settings. Unlike previous reports, we also highlighted the contribution of sex.
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2023.1152204
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Article: "Self-Neuroenhancement": The Last Frontier of Noninvasive Brain Stimulation?

Fisicaro, Francesco / Lanza, Giuseppe / Bella, Rita / Pennisi, Manuela

Journal of clinical neurology (Seoul, Korea)

2020 Volume 16, Issue 1, Page(s) 158–159

Language	English
Publishing date	2020-01-16
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2500489-X
ISSN	2005-5013 ; 1738-6586
ISSN (online)	2005-5013
ISSN	1738-6586
DOI	10.3988/jcn.2020.16.1.158
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Article: Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study.

Fisicaro, Francesco / Lanza, Giuseppe / D'Agate, Carmela Cinzia / Pennisi, Manuela / Cantone, Mariagiovanna / Pennisi, Giovanni / Hadjivassiliou, Marios / Bella, Rita

Frontiers in human neuroscience

2022 Volume 16, Page(s) 931727

Abstract: Background: Sonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler ... ...

Abstract	Background: Sonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography. Materials and methods: Montreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT). Results: Worse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted. Conclusion: These treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement.
Language	English
Publishing date	2022-09-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2022.931727
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Article ; Online: Daily mocha coffee intake and psycho-cognitive status in non-demented non-smokers subjects with subcortical ischaemic vascular disease.

Fisicaro, Francesco / Lanza, Giuseppe / Pennisi, Manuela / Vagli, Carla / Cantone, Mariagiovanna / Falzone, Luca / Pennisi, Giovanni / Ferri, Raffaele / Bella, Rita

International journal of food sciences and nutrition

2022 Volume 73, Issue 6, Page(s) 821–828

Abstract: Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), ... ...

Abstract	Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.
MeSH term(s)	Activities of Daily Living ; Coffee ; Cognition ; Humans ; Non-Smokers ; Vascular Diseases
Chemical Substances	Coffee
Language	English
Publishing date	2022-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1121877-0
ISSN	1465-3478 ; 0963-7486
ISSN (online)	1465-3478
ISSN	0963-7486
DOI	10.1080/09637486.2022.2050999
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Article: Impact of Stain Normalization on Pathologist Assessment of Prostate Cancer: A Comparative Study.

Salvi, Massimo / Caputo, Alessandro / Balmativola, Davide / Scotto, Manuela / Pennisi, Orazio / Michielli, Nicola / Mogetta, Alessandro / Molinari, Filippo / Fraggetta, Filippo

Cancers

2023 Volume 15, Issue 5

Abstract: In clinical routine, the quality of whole-slide images plays a key role in the pathologist's diagnosis, and suboptimal staining may be a limiting factor. The stain normalization process helps to solve this problem through the standardization of color ... ...

Abstract	In clinical routine, the quality of whole-slide images plays a key role in the pathologist's diagnosis, and suboptimal staining may be a limiting factor. The stain normalization process helps to solve this problem through the standardization of color appearance of a source image with respect to a target image with optimal chromatic features. The analysis is focused on the evaluation of the following parameters assessed by two experts on original and normalized slides: (i) perceived color quality, (ii) diagnosis for the patient, (iii) diagnostic confidence and (iv) time required for diagnosis. Results show a statistically significant increase in color quality in the normalized images for both experts (
Language	English
Publishing date	2023-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15051503
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Article: Interdisciplinary Multidimensional Assessment of Transthyretin Amyloidosis before and after Tafamidis.

Pennisi, Manuela / Lanza, Giuseppe / Vitello, Girolamo Aurelio / Faro, Denise Cristiana / Fisicaro, Francesco / Cappellani, Francesco / Bella, Rita / Monte, Ines Paola

Life (Basel, Switzerland)

2023 Volume 13, Issue 12

Abstract: Background: Clinically, there is considerable heterogeneity in the presentation of transthyretin amyloidosis (ATTR), which ranges from primarily cardiac and primarily neurologic to mixed disease, among other manifestations. Because of this complex ... ...

Abstract	Background: Clinically, there is considerable heterogeneity in the presentation of transthyretin amyloidosis (ATTR), which ranges from primarily cardiac and primarily neurologic to mixed disease, among other manifestations. Because of this complex presentation, the diagnosis and management of patients with ATTR are often challenging and should be performed in interdisciplinary centers specialized in amyloidosis. Here, we aimed to increase awareness of ATTR detection and pathophysiology through a multidimensional multiorgan approach. Case report: We reported on a 60-year-old man with wild-type ATTR who underwent a number of both basic and advanced cardiological and neurological investigations at baseline and after a treatment period with the TTR tetramer stabilizer, tafamidis. Several findings are provided here, some of which might be considered instrumental correlates of the patient's clinical improvement after therapy. Conclusions: Adequate awareness and prompt recognition of ATTR support early diagnosis and faster access to therapies, thereby slowing the progression and improving the prognosis. The need for a multidisciplinary alliance between specialists and the opportunity to perform, at least in selected cases, a set of specific examinations for a detailed assessment of ATTR patients can also provide valuable insights into the physiopathology and response to therapy of a disease as complex and intriguing as ATTR.
Language	English
Publishing date	2023-12-07
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13122305
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Article ; Online: Transcriptional upregulation of galectin-3 in multiple sclerosis.

Mangano, Katia / Petralia, Maria Cristina / Bella, Rita / Pennisi, Manuela / Muñoz-Valle, José Francisco / Hernández-Bello, Jorge / Nicoletti, Ferdinando / Fagone, Paolo

Immunologic research

2023 Volume 71, Issue 6, Page(s) 950–958

Abstract: Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of the central nervous system (CNS) affecting approximately 2.5 million people worldwide. The mechanisms underlying the pathogenesis of MS are still only partially elucidated. Galectins are ...

Abstract	Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of the central nervous system (CNS) affecting approximately 2.5 million people worldwide. The mechanisms underlying the pathogenesis of MS are still only partially elucidated. Galectins are a family of β-galactoside-binding lectins that are involved in the regulation of immune and inflammatory responses and have been shown to exert a role in the maintenance of central nervous system (CNS) homeostasis. There has been an increasing interest in the role of galectin-3 in neuroinflammation and neurodegeneration. In the current study, we have evaluated the expression levels of galectin-3 in different cellular populations involved in the etiopathogenesis of MS. We have observed dramatically higher transcriptomic levels of galectin-3 in encephalitogenic CD4+ T cells in a preclinical model of MS, the MOG-induced experimental allergic encephalomyelitis (EAE). Also, significantly higher levels of galectin-3 were found in microglial cells, astrocytes, and oligodendrocytes isolated from the spinal cord of EAE mice, as well as in human MS-related white matter lesions. Modular co-expression analysis revealed that galectin-3 is co-expressed with genes involved in the regulation of microglia, cytokine production, and chemotaxis. This is the first comprehensive analysis of the expression of galectin-3 in MS, further strengthening its potential pathogenetic role in the etiopathogenesis of this CNS autoimmune disorder.
MeSH term(s)	Animals ; Humans ; Mice ; Encephalomyelitis, Autoimmune, Experimental ; Galectin 3/genetics ; Galectin 3/metabolism ; Galectins/genetics ; Galectins/metabolism ; Mice, Inbred C57BL ; Multiple Sclerosis ; Up-Regulation
Chemical Substances	Galectin 3 ; Galectins ; Lgals3 protein, mouse
Language	English
Publishing date	2023-07-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	632857-x
ISSN	1559-0755 ; 0257-277X
ISSN (online)	1559-0755
ISSN	0257-277X
DOI	10.1007/s12026-023-09408-x
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