Francesca Pescini - Academia.edu (original) (raw)

Papers by Francesca Pescini

Cambridge University Press eBooks, Jun 9, 2014

Circulation-cardiovascular Imaging, 2020

January 2020 1 Benedetta Formelli, MD Antonio Farina, MD Francesca Pescini, PhD, MD Vanessa Palum... more January 2020 1 Benedetta Formelli, MD Antonio Farina, MD Francesca Pescini, PhD, MD Vanessa Palumbo, PhD, MD Maria Grazia D’Alfonso, MD Andrea Oddo, MD Fabio Mori, MD Anna Poggesi, PhD, MD Cardiac calcified amorphous tumor (CAT) is a rare benign intracavitary mass, composed of nodular calcium deposits within fibrinous material.1 The most common locations are left ventricle and mitral valve, but it may occur in any chamber of the heart.2 Only few cases have been reported in literature, so incidence, pathogenesis and natural history of CAT are not well characterized. Herein, we report a case of CAT diagnosed after an ischemic stroke.

Journal of the Neurological Sciences, Aug 1, 2009

Acta Neurologica Scandinavica, Mar 26, 2015

CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leadi... more CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype. Altogether, 134 Finnish CADASIL patients with p.Arg133Cys mutation were analysed for possible associations between the apolipoprotein E (APOE) genotype, angiotensinogen (AGT) p.Met268Thr polymorphism or neutral p.Ala202Ala NOTCH3 polymorphism and earlier first-ever stroke or migraine. We found no association between the APOE genotypes, AGT polymorphism, NOTCH3 polymorphism and earlier first-ever stroke or migraine. The APOE, AGT and NOTCH3 polymorphism did not modify the onset of strokes or migraine in our CADASIL sample, which is one of the largest mutationally homogenous CADASIL populations published to date. International collaboration, pooled analyses and genomewide approaches are warranted to identify the genetic factors that modify the highly variable CADASIL phenotype.

n/a, 2013

There are few studies in literature regarding the differential diagnosis between syncope and epil... more There are few studies in literature regarding the differential diagnosis between syncope and epilepsy in patients with transient loss of consciousness (T-LOC) of uncertain etiology. Data obtained on few patients, however, seem to show a common "misdiagnosis" of epilepsy (20-30%) in patients with episodes of T-LOC likely to be syncope. For this reason the Italian Group of Syncope in the elderly (GIS) of the Italian Society of Gerontology and Geriatrics has started multicenter study (Overlapping Between Epilepsy and Syncope Study), with the primary purpose to evaluate the efficiency of cardiovascular tests and neuroautonomic assessments in patients diagnosed with T-LOC of epileptic origin and recurrences despite drug therapy, and as a secondary aim, to evaluate the diagnostic and therapeutic impact of the intervention in terms of recurrence of loss of consciousness

Aging Clinical and Experimental Research, May 30, 2019

Background Vascular cognitive impairment (VCI) is an extremely disabling condition that includes ... more Background Vascular cognitive impairment (VCI) is an extremely disabling condition that includes post-stroke dementia and VCI caused by cerebral small vessel disease (SVD). Currently, there is no approved treatment for this condition. Drugs active on the cholinergic pathway have been tested in VCI patients showing positive but limited efficacy. The calcium-antagonist nimodipine also showed some moderate positive effects in VCI patients. Aims CONIVaD (choline alphoscerate and nimodipine in vascular dementia) is a pilot, single-center, double-blinded, randomized trial aimed to assess whether the association of choline alphoscerate and nimodipine is more effective than nimodipine alone in reducing cognitive decline in patients with SVD and mild-to-moderate cognitive impairment. Methods All patients are evaluated at baseline and after 12 months with: (1) clinical, daily functions, quality of life, and mood assessment and (2) extensive neuropsychological evaluation. After the baseline evaluation, patients are randomly assigned to one of the two arms of treatment: (1) nimodipine 90 mg/die t.i.d plus placebo b.i.d and (2) nimodipine 90 mg t.i.d plus choline alphoscerate 1200 mg/die b.i.d. for a total of 12 months. The primary endpoint is cognitive decline, expressed as the loss of at least two points on the Montreal Cognitive Assessment at 12 months. Secondary endpoints include safety and tolerability, functional, quality of life, and neuropsychological measures. Discussion CONIVaD study is the first randomized controlled trial to examine the cognitive efficacy of combined choline alphoscerate-nimodipine treatment in VCI patients. Results of this pilot study will serve as a methodological basis for other clinical controlled, multicentric, double-blinded, and randomized trials. Trial registration Clinical Trial NCT03228498. Registered 25 July 2017. Keywords Vascular cognitive impairment • Small vessel disease • Therapy • Choline alphoscerate • Nimodipine • MoCA Background Vascular cognitive impairment (VCI) is an extremely disabling condition with severe consequences in terms of direct (e.g., visits, prescriptions, hospital admissions, etc.) and indirect costs (e.g., loss of patient's and caregiver's Emilia Salvadori and Anna Poggesi contributed equally to this work.

Journal of Headache and Pain, Feb 25, 2012

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADAS... more Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by NOTCH3 mutations. It is characterized by migraine, with or without aura, ischemic events, psychiatric and cognitive disturbances. There is no approved treatment for migraine prophylaxis in CADASIL, but acetazolamide has been anecdotally reported to be effective. We retrospectively reviewed our database of patients with a genetic diagnosis of CADASIL to identify how many of them were treated with acetazolamide for the prophylaxis of migraine. The efficacy and the tolerability of this treatment were checked looking at the clinic reports. Acetazolamide was prescribed in seven patients; the mean duration of treatment was 6 months, and the daily dose ranged from 125 to 500 mg. Three patients had a total and sustained remission, while in two patients a reduction in attacks and an improvement of the headache intensity were recorded. In one of these, acetazolamide was deliberately taken only during the migraine attack and the beneficial effect started 1 h after administration. In two patients, the drug did not produce any beneficial effect. Mild side effects were recorded in two patients. Our preliminary experience expands previous reports and confirms the possible efficacy of acetazolamide in CADASIL migraine. Based on these data, a randomized controlled trial seems worthy to be carried out to test the efficacy and safety of this drug.

European Heart Journal, Nov 1, 2020

European Journal of Neurology, 2009

Journal of Neurology, Jul 24, 2011

We read with interest the paper by Gong et al. [1] on the clinical and genetic features of a cere... more We read with interest the paper by Gong et al. [1] on the clinical and genetic features of a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) family with high values of lipoprotein(a) [Lp(a)]. They concluded that elevated Lp(a) levels might have contributed to the cerebrovascular phenotype in their family. We would like to report our three CADASIL families with elevated Lp(a) levels (Table 1). The mutations, all different from that reported by Gong and colleagues [1], are reported in Table 1. Lp(a) levels were measured for various reasons in eight members of these CADASIL families by the same laboratory, and found elevated in seven (Table 1) (one patient already reported) [2]. Patients had various association of other vascular risk factors. Symptomatic patients showed the typical clinical manifestations of the disease. Cerebral MRI picture was that typical of the disease, with different severity degrees of white matter lesions, also in accordance with the subjects’ ages. In only one of the patients with a history of stroke or in those who underwent vessel evaluation (ultrasound, MR angiography, or digital subtraction angiography) was evidence of large vessel pathology found. One 70-year-old man with dyslipidemia had mild carotid atherosclerosis. All the strokes were of the lacunar type, and no nonlacunar infarct was detected on cerebral MRI. In one patient, MRI revealed a cerebellar arteriovenous malformation, which was later found associated on digital subtraction angiography with a vertebral artery aneurysm. This case has already been reported [3]. All the members of these families have now been followed up for more than 10 years. In conclusion, we did not find clinical or radiological features suggestive of significant large vessel disease in any of our patients affected by CADASIL and with elevated Lp(a) levels. In our opinion, the finding of elevated Lp(a) levels in NOTCH3 mutations carriers seems to be incidental, of doubtful clinical significance, and does not appear to contribute to the cerebrovascular phenotype. However, our data are too limited to get definitive conclusions. While an elevated Lp(a) level is known as a risk factor for ischemic heart disease, its role is less clearly defined in cerebrovascular diseases [4]. In the recent Guidelines for the Primary Prevention of Stroke, elevation of Lp(a) level was included among the less well documented cerebrovascular risk factors (recommendation for treatment in primary prevention of ischemic stroke: class IIb; level of evidence B) [4]. Considering our small series and also Gong et al.’s report in which only one family member presented with large vessel pathology, we believe that systematic screening for elevated Lp(a) levels in CADASIL patients is not recommended. A few cases of large vessel pathology have been reported in this small vessel disease [5]. The value of Lp(a) levels evaluation in these patients remains to be elucidated. R. Valenti and S. Nannucci contributed equally to this work.

Neurological Sciences, Apr 4, 2017

Besides its well known function on bone metabolism, vitamin D role in cerebrovascular pathologies... more Besides its well known function on bone metabolism, vitamin D role in cerebrovascular pathologies including cerebral small vessel disease has been confirmed by recent meta-analysis. In this study, we measured vitamin D levels in 56 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients (mean age 49.9) with no or minimal disability (modified Ranking Score, mRS B2) and in 56 age, sex and seasonality matched healthy controls. History of ischemic events was recorded and cognitive functions were assessed using the Mini-Mental State Examination. White matter hyperintensities on brain T2-weighted magnetic resonance images were classified according to a modified Fazekas scale. Comparison of vitamin D levels between patients and controls showed significant lower values (p \ 0.05) in no-to-mild CADASIL patients and a higher number of subjects with severe deficiency [25(OH)D \10 ng/ml]. Vitamin D levels did not correlate with vascular risk factors, clinical data or Fazekas score. The role of vitamin D is worth to be further explored in prospective studies.

Drugs & Aging, Apr 15, 2021

Background No approved treatment is available for patients with vascular cognitive impairment (VC... more Background No approved treatment is available for patients with vascular cognitive impairment (VCI) due to cerebral small vessel disease (SVD). Objective The CONIVaD (Choline Alphoscerate and Nimodipine in Vascular Dementia) study aimed to investigate the feasibility, efficacy, and safety of a combined treatment with choline alphoscerate and nimodipine in patients with SVD and mild-to-moderate cognitive impairment. Methods Within this pilot, single-center (university hospital), double-blinded, randomized clinical trial, patients were randomized to two arms: 1-year treatment with nimodipine 30 mg three times a day (TID) plus choline alphoscerate 600 mg twice a day (BID) (arm 1) or nimodipine 30 mg TID plus placebo BID (arm 2). Patients underwent an evaluation at baseline and after 12 months. Cognitive decline, defined as a ≥ 2-point loss on the Montreal Cognitive Assessment, was the primary endpoint. Functional, quality of life, other cognitive measures, and safety were secondary endpoints. Treatment adherence was measured by the count of medicine bottles returned by patients. Results Sixty-two patients were randomized (31 each arm). Fourteen patients (22%) dropped out for reasons including consent withdrawal (n = 9), adverse reactions (n = 4), and stroke (n = 1). Forty-eight patients (mean ± SD age 75.1 ± 6.8 years), well balanced between arms, completed the study. Regarding adherence, of the prescribed total drug dose, > 75% was taken by 96% of patients for choline alphoscerate, 87.5% for placebo, and 15% for nimodipine. No statistically significant differences were found between the treatment groups for the primary cognitive outcome, nor for the secondary outcomes. Eight patients had non-serious adverse reactions; five presented adverse events. Conclusion Patients' adherence to treatment was low. With this limitation, the combined choline alphoscerate-nimodipine treatment showed no significant effect in our cohort of VCI patients with SVD. The safety profile was good overall.

Acta Psychiatrica Scandinavica, Sep 1, 2005

Journal of Neurology, Oct 26, 2014

The objective of the study is to detail clinical and NOTCH3 gene mutational spectrum in a large g... more The objective of the study is to detail clinical and NOTCH3 gene mutational spectrum in a large group of Italian CADASIL patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial cerebral small vessels disease caused by mutations in the NOTCH3 gene on 19p13 usually presenting in young or middle adulthood. Characteristic features include migraine, recurrent lacunar stroke, subcortical dementia, mood disturbances and leukoencephalopathy. The disorder is often overlooked and misdiagnosed. CADASIL prevalence and disease burden is still undetermined. We retrospectively reviewed demographic, clinical, and mutational characteristic of all CADASIL patients diagnosed from January 2002 to December 2012 in three referral centers for neurogenetic and cerebrovascular diseases in central Italy. 229 NOTCH3 positive subjects were identified. Mean age at diagnosis was 57.8 ± 14.7 years, and 48.6 ± 17.1 years at first symptom onset. Most frequent clinical symptoms were ischemic events (59 %) and psychiatric disturbances (48 %). The highest percentage of mutations were found on exons 4 and 19 (20.6 and 17.6 % respectively), the remaining being dispersed over the entire EGF-like region of the NOTCH3 gene. 209 patients resided in a circumscribed geographic area which included three regions of the central Italy, yielding a minimum prevalence of 4.1 per 100.000 adult inhabitants. This is the most extensive study on CADASIL in Italy. Clinical phenotype showed several peculiarities in frequency and presentation of the main disease manifestations. Our study enlarges the number of pathogenic NOTCH3 mutations and due to the heterogeneous mutational spectrum observed suggests that full sequencing of exons 2-24 is mandatory for CADASIL screening in the Italian population.

Stroke, Nov 1, 2012

C erebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADA... more C erebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; MIM 125310) is an autosomal-dominant small-vessel disease (SVD) caused by highly stereotyped mutations on exons 2 to 23 of the NOTCH3 gene. 1,2 The disease is characterized by migraine, frequently with aura, transient ischemic attacks and/or strokes, mood disorders, and cognitive decline leading progressively to dementia and disability. 3 However, the clinical picture may be extremely variable and some patients present few disturbances and a milder course even at old age. 4,5 Typical neuroimaging features are severe leukoencephalopathy, frequently involving the temporal pole and the external capsule, lacunar lesions, and microbleeds. 6-11 Also the neuroimaging picture may be variable, particularly in the initial stages. 12 Overall, the recognition of the disease before the development of the full clinical-neuroimaging picture may be challenging. Moreover, as we recently reported, none of the Background and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) phenotype is highly variable, and, although the full clinical-neuroimaging picture may be suggestive of the disease, no characteristic is pathognomonic. Thus, a genetic test remains the diagnostic gold standard, but because it is costly and time-consuming, a pregenetic screening appears desirable. We aimed at developing the CADASIL scale, a screening tool to be applied in the clinical setting. Methods-A preliminary scale was created assigning weighted scores to common disease features based on their frequencies obtained in a pooled analysis of selected international CADASIL series. The accuracy of the scale versus the genetic diagnosis was tested with receiver operating characteristic analysis after the application of this scale to 61 CADASIL and 54 NOTCH3-negative patients (no pathogenic mutation on exons 2-23 of the NOTCH3 gene). To improve the scale accuracy, we then developed an ad hoc optimization algorithm to detect the definitive scale. A third group of 39 patients affected by sporadic small-vessel disease was finally included in the algorithm to evaluate the stability of the scale. Results-The cutoff score of the definitive CADASIL scale had a sensitivity of 96.7% and a specificity of 74.2%. This scale was robust to contamination of patients with sporadic small-vessel disease. Conclusions-The CADASIL scale is a simple and sufficiently accurate screening tool to select patients with a high probability to be affected by the disease and therefore to be subjected to the genetic testing.

European Journal of Neurology, Feb 5, 2023

Background and purposeThe multifactorial relationship between atrial fibrillation (AF) and cognit... more Background and purposeThe multifactorial relationship between atrial fibrillation (AF) and cognitive impairment needs to be elucidated. The aim of this study was to assess, in AF patients on oral anticoagulants (OACs), the prevalence of cognitive impairment, defined according to clinical criteria or data‐driven phenotypes, the prevalence of cognitive worsening, and factors associated with cognitive outcomes.MethodsThe observational prospective Strat‐AF study enrolled AF patients aged ≥ 65 years who were receiving OACs. The baseline and 18‐month protocol included clinical, functional, and cognitive assessment, and brain magnetic resonance imaging. Cognitive outcomes were: empirically derived cognitive phenotypes; clinical diagnosis of cognitive impairment; and longitudinal cognitive worsening.ResultsOut of 182 patients (mean age 77.7 ± 6.7 years, 63% males), 82 (45%) received a cognitive impairment diagnosis, which was associated with lower education level and functional status, and higher level of atrophy. Cluster analysis identified three cognitive profiles: dysexecutive (17%); amnestic (25%); and normal (58%). Compared to the normal group, the dysexecutive group was older, and had higher CHA2DS2‐VASc scores, while the amnestic group had worse cognitive and functional abilities, and medial temporal lobe atrophy (MTA). Out of 128 followed‐up patients, 35 (27%) had cognitive worsening that was associated with lower education level, worse cognitive efficiency, CHA2DS2‐VASc score, timing of OAC intake, history of stroke, diabetes, non‐lacunar infarcts, white matter hyperintensities and MTA. In multivariate models, belonging to the dysexecutive or amnestic group was a main predictor of cognitive worsening.ConclusionsIn our cohort of older AF patients, CHA2DS2‐VASc score, timing of OAC intake, and history of stroke influenced presence, type and progression of cognitive impairment. Empirically derived cognitive classification identified three groups with different clinical profiles and better predictive ability for cognitive worsening compared to conventional clinical diagnosis.

Frontiers in Neurology, May 13, 2022

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic ri... more Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65-74 years and sex category (CHA 2 DS 2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of "asymptomatic" brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA 2 DS 2-VASc and HAS-BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition Bianconi et al. CHA2DS2-VASc, HAS-BLED, AF: Brain MRI of cognitive scores. The addition of motor and depressive scores to CHA 2 DS 2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar-infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification.