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Cerebrovascular diseases (CVDs) are one leading cause of morbidity and mortality worldwide. Despite intensive investigations, more than 30% of strokes remain of undetermined origin. Rare Cerebrovascular Diseases (rCVDs), including heritable (i.e., CADASIL, COL4A1 syndrome, Fabry disease) and acquired conditions (i.e., Sneddon syndrome, Moyamoya arteriopathy) account for a proportion of these strokes. However, rCVDs are often misdiagnosed since clinicians are not able to recognize them. Although rare, the identification of these stroke causes is important to establish appropriate management measures, including genetic counselling, and, if available, therapy. The lack of data on phenotype and clinical course of rCVDs, given the paucity of published series, makes the diagnosis and the development of therapies challenging. Furthermore, the molecular characterization of rCVDs is still lacking, despite progresses achieved in common stroke by applying high throughput approaches as multi-omics. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, clinical and research activities are usually reserved to few specialized centers, mostly located in the North of Italy, leading patients to expensive trips for consultations. Therefore, the creation of a clinical and research network aimed at improving the diagnostic pathways of rCVDs is highly needed to improve the number of patients with rCVDs to better define the clinical phenotype and to transfer the knowledge on rCVDs in other centers overall Italy filling the geographical gap affecting Southern Italy.
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| Measure | Description | Time Frame |
|---|---|---|
| Describe the phenotypic characteristics of rCVD patients | To describe the phenotypic characteristics of rCVD patients. All patients will complete a standardized neurological assessment consisting of anamnestic data collection (family history of neurological pathology, and in particular of rCVD, cardiovascular risk factors, medications taken, comorbidities, recent or previous head injuries) and a complete physical examination. | 0-12 months |
| Assess the natural history of disease | To develop a new, unique, and large registry on rCVDs recruiting a large number of patients (500) , patients will be recruited by all the participating clinical centers | 0-12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Identify the molecular mechanisms | Identify the molecular mechanisms underlying rCVD, targeted/quantitative approaches will validate the emerged key molecular features (e.g by transcriptomic, proteomic, metabolomic, and lipidomic approaches). | 12-30 months |
| Identify biomarkers |
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Inclusion Criteria:
Exclusion Criteria:
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Adults, male and female patients affected by a Rare Cerebrovascular Disease (rCVD)
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Bersano, MD | Contact | + 39 02.2394 | anna.bersano@istituto-besta.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ospedale Regionale Generale "F. Miulli", Acquaviva delle Fonti | Recruiting | Acquaviva delle Fonti | BA | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34756108 | Background | Caponnetto V, Ornello R, De Matteis E, Papavero SC, Fracasso A, Di Vito G, Lancia L, Ferrara FM, Sacco S. The COVID-19 Pandemic as an Opportunity to Improve Health Care Through a Nurse-Coordinated Multidisciplinary Model in a Headache Specialist Center: The Implementation of a Telemedicine Protocol. Telemed J E Health. 2022 Jul;28(7):1016-1022. doi: 10.1089/tmj.2021.0414. Epub 2021 Nov 9. | |
| 34548610 |
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Identify reliable and usable circulating biomarkers for the diagnosis of rCVD by applying mass spectrometry-based cutting-edge technologies for an unbiased identification of differentially abundant candidates (e.g. proteins or metabolites), and for their validation and simultaneous assessment in multi-marker panels |
| 12-30 months |
| Provide the best clinical and therapeutic management | Implement the virtual multi-specialty and multicenter rCVD case-sharing model in order to provide the best clinical and therapeutic management of the patients taken in. A team of specialists with expertise in each rCVD, comprising neurologists, neurosurgeons, neuro-radiologists, interventional radiologists, neuropsychiatrists, geneticists, neurophysiologists and/or psychologists, will schedule virtual monthly meetings to discuss the diagnosis and provide individual patients with the best diagnostic and management paths. A specific platform for second opinion consultations will be created by using the existing telemedicine platform. | 12-30 months |
| ASST Melegnano Martesana | Recruiting | Melegnano | MI | Italy |
|
| Neurologia Stroke Unit dell'Asst Rhodense | Recruiting | Rho | Mi | Italy |
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| Fondazione Istituto G. Giglio, Cefalù | Recruiting | Cefalù | PA | Italy |
|
| UO Neurologia degli Ospedali di Cesena e Forlì, Ospedale Bufalini Cesena ed Ospedale Morgagni-Pierantoni (Ausl della Romagna) | Recruiting | Cesena | Italy |
|
| ASST di Cremona | Recruiting | Cremona | Italy |
|
| Ospedale "Spaziani" di Frosinone | Recruiting | Frosinone | Italy |
|
| U.O. Neurologia, Ospedale Sant'Andrea, La Spezia | Recruiting | La Spezia | Italy |
|
| ASST Grande Ospedale Metropolitano Niguarda | Recruiting | Milan | Italy |
|
| Fondazione IRCCS Istituto Neurologico Carlo Besta | Recruiting | Milan | Italy |
|
| Ospedale Luigi Sacco, ASST Fatebenefratelli Sacco | Recruiting | Milan | Italy |
|
| Stroke Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano | Recruiting | Milan | Italy |
|
| IRCCS Policlinico San Matteo, Pavia | Recruiting | Pavia | Italy |
|
| Neurologia d'Urgenza e Stroke Unit dell'Ospedale di Pescara | Recruiting | Pescara | Italy |
|
| Neurologia dell'Ospedale Sandro Pertini - ASL Roma2 | Recruiting | Roma | Italy |
|
| Policlinico Tor Vergata, UOSD Stroke Unit | Recruiting | Roma | Italy |
|
| Neurologia PO Levante Asl 2 Savonese | Recruiting | Savona | Italy |
|
| Background |
| Banfi C, Baetta R, Barbieri SS, Brioschi M, Guarino A, Ghilardi S, Sandrini L, Eligini S, Polvani G, Bergman O, Eriksson P, Tremoli E. Prenylcysteine oxidase 1, an emerging player in atherosclerosis. Commun Biol. 2021 Sep 21;4(1):1109. doi: 10.1038/s42003-021-02630-z. |
| 28143922 | Background | Degan D, Ornello R, Tiseo C, De Santis F, Pistoia F, Carolei A, Sacco S. Epidemiology of Transient Ischemic Attacks Using Time- or Tissue-Based Definitions: A Population-Based Study. Stroke. 2017 Mar;48(3):530-536. doi: 10.1161/STROKEAHA.116.015417. Epub 2017 Jan 31. |
| 19038914 | Background | Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009 Feb;40(2):394-9. doi: 10.1161/STROKEAHA.108.523209. Epub 2008 Nov 26. |
| 34609660 | Background | Romani I, Nencini P, Sarti C, Pracucci G, Zedde M, Nucera A, Cianci V, Moller J, Toni D, Orsucci D, Casella C, Pinto V, Palumbo P, Barbarini L, Bella R, Ragno M, Scoditti U, Mezzapesa DM, Tassi R, Diomedi M, Cavallini A, Volpi G, Chiti A, Bigliardi G, Sacco S, Linoli G, Ricci S, Giordano A, Bonetti B, Rasura M, Cecconi E, Princiotta Cariddi L, Curro Dossi R, Melis M, Consoli D, Guidetti D, Biagini S, Accavone D, Inzitari D. Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol. Neurol Sci. 2022 Apr;43(4):2433-2439. doi: 10.1007/s10072-021-05615-2. Epub 2021 Oct 5. |
| 27245348 | Background | Bersano A, Markus HS, Quaglini S, Arbustini E, Lanfranconi S, Micieli G, Boncoraglio GB, Taroni F, Gellera C, Baratta S, Penco S, Mosca L, Grasso M, Carrera P, Ferrari M, Cereda C, Grieco G, Corti S, Ronchi D, Bassi MT, Obici L, Parati EA, Pezzini A, De Lodovici ML, Verrengia EP, Bono G, Mazucchelli F, Zarcone D, Calloni MV, Perrone P, Bordo BM, Colombo A, Padovani A, Cavallini A, Beretta S, Ferrarese C, Motto C, Agostoni E, Molini G, Sasanelli F, Corato M, Marcheselli S, Sessa M, Comi G, Checcarelli N, Guidotti M, Uccellini D, Capitani E, Tancredi L, Arnaboldi M, Incorvaia B, Tadeo CS, Fusi L, Grampa G, Merlini G, Trobia N, Comi GP, Braga M, Vitali P, Baron P, Grond-Ginsbach C, Candelise L; Lombardia GENS Group*. Clinical Pregenetic Screening for Stroke Monogenic Diseases: Results From Lombardia GENS Registry. Stroke. 2016 Jul;47(7):1702-9. doi: 10.1161/STROKEAHA.115.012281. Epub 2016 May 31. |
| 30311053 | Background | Bersano A, Bedini G, Markus HS, Vitali P, Colli-Tibaldi E, Taroni F, Gellera C, Baratta S, Mosca L, Carrera P, Ferrari M, Cereda C, Grieco G, Lanfranconi S, Mazucchelli F, Zarcone D, De Lodovici ML, Bono G, Boncoraglio GB, Parati EA, Calloni MV, Perrone P, Bordo BM, Motto C, Agostoni E, Pezzini A, Padovani A, Micieli G, Cavallini A, Molini G, Sasanelli F, Sessa M, Comi G, Checcarelli N, Carmerlingo M, Corato M, Marcheselli S, Fusi L, Grampa G, Uccellini D, Beretta S, Ferrarese C, Incorvaia B, Tadeo CS, Adobbati L, Silani V, Farago G, Trobia N, Grond-Ginsbach C, Candelise L; Lombardia GENS-group. The role of clinical and neuroimaging features in the diagnosis of CADASIL. J Neurol. 2018 Dec;265(12):2934-2943. doi: 10.1007/s00415-018-9072-8. Epub 2018 Oct 11. |
| 30604336 | Background | Bersano A, Bedini G, Nava S, Acerbi F, Sebastiano DR, Binelli S, Franceschetti S, Farago G, Grisoli M, Gioppo A, Ferroli P, Bruzzone MG, Riva D, Ciceri E, Pantaleoni C, Saletti V, Esposito S, Nardocci N, Zibordi F, Caputi L, Marzoli SB, Zedde ML, Pavanello M, Raso A, Capra V, Pantoni L, Sarti C, Pezzini A, Caria F, Dell' Acqua ML, Zini A, Baracchini C, Farina F, Sanguigni S, De Lodovici ML, Bono G, Capone F, Di Lazzaro V, Lanfranconi S, Toscano M, Di Piero V, Sacco S, Carolei A, Toni D, Paciaroni M, Caso V, Perrone P, Calloni MV, Romani A, Cenzato M, Fratianni A, Ciusani E, Prontera P, Lasserve ET, Blecharz K, Vajkoczy P, Parati EA; GEN-O-MA study group. GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease-study protocol and preliminary results. Neurol Sci. 2019 Mar;40(3):561-570. doi: 10.1007/s10072-018-3664-z. Epub 2019 Jan 3. |
| 27084221 | Background | Bersano A, Morbin M, Ciceri E, Bedini G, Berlit P, Herold M, Saccucci S, Fugnanesi V, Nordmeyer H, Farago G, Savoiardo M, Taroni F, Carriero M, Boncoraglio Giorgio B, Perucca L, Caputi L, Parati Eugenio A, Kraemer M. The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review. J Neurol Sci. 2016 May 15;364:77-83. doi: 10.1016/j.jns.2016.03.011. Epub 2016 Mar 5. |
| 30519889 | Background | Panara V, Navarra R, Mattei PA, Piccirilli E, Bartoletti V, Uncini A, Caulo M. Correlations between cervical spinal cord magnetic resonance diffusion tensor and diffusion kurtosis imaging metrics and motor performance in patients with chronic ischemic brain lesions of the corticospinal tract. Neuroradiology. 2019 Feb;61(2):175-182. doi: 10.1007/s00234-018-2139-5. Epub 2018 Dec 5. |
| ID | Term |
|---|---|
| D046589 | CADASIL |
| D004194 | Disease |
| D009072 | Moyamoya Disease |
| D018860 | Sneddon Syndrome |
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D002544 | Cerebral Infarction |
| D020520 | Brain Infarction |
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D015140 | Dementia, Vascular |
| D002539 | Cerebral Arterial Diseases |
| D020765 | Intracranial Arterial Diseases |
| D020521 | Stroke |
| D003704 | Dementia |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D002340 | Carotid Artery Diseases |
| D001157 | Arterial Occlusive Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D040181 | Genetic Diseases, X-Linked |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
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