INVOLVEMENT OF THE CEREBELLUM IN CEREBRAL AMYLOID ANGIOPATHY

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere: Angiopatia amiloidă cerebrală (AAC) este caracterizată prin depozite de amiloid beta în vasele creierului și leptomeningelui. Hemoragia intracerebrală (HI) lobară este semnul clinic al angiopatiei amiloide. Se presupune că un subgrup de hemoragii localizate în cerebel sunt asociate cu AAC. Scopul lucrării: Analiza implicării cerebelului în angiopatia amiloidă cerebrală. Materiale și metode: Au fost selectați pacienții cu hemoragie intracerebrală spontane investigați imagistic prin rezonanță magnetică. Au fost analizați retrospectiv pacienții internați în perioada 20092015 și prospectiv în perioada 2015-2019. Pacienții au fost diagnosticați cu AAC conform criteriilor Boston. Au fost analizate pattern-ul distribuției microhemoragiilor, modificările substanței albe și capacitățile cognitive ale pacienților cu și fără implicarea cerebelului. Rezultate: Din totalul de 718 pacienți, 189 (26,3%) au fost examinați prin IRM cerebrală. Doar 155 pacienți au îndeplinit criteriile Boston pentru diagnosticul de AAC. Pacienții cu AAC și implicarea cerebelului sunt mai tineri (67 +-6 ani vs 72+-10 ani, p < 0.001), și au mai multe microhemoragii comparativ cu pacienții cu ACC fără implicarea cerebelului, 33+-23 vs. 3+-9, p < 0.001. La pacienții cu implicarea cerebelului s-a înregistrat un grad mai sever de afectare a substanței albe conform scalei Fazekas, și o prevalență mai mare a dereglărilor cognitive, 26% versus 3.6%, p < 0.001. Concluzie: implicarea cerebelară nu este rară în AAC. Majoritatea pacienților prezintă microhemoragii cerebelare și hemoragii multiple, au un pattern microvascular mai agresiv, cu dereglările cognitive sunt mai proeminente.Introduction. Cerebral amyloid angiopathy (CAA) is characterized by deposits of beta amyloid in small and medium-sized vessels of the brain and leptomeninges. Lobar hemorrhage is a primary clinical sign of CAA. A subset of hemorrhages located in the cerebellum are thought to be associated with amyloid storage. Aim of the study. Analysis of the involvement of the cerebellum in CAA. Materials and methods. Patients with spontaneous intracerebral hemorrhage that were investigated by magnetic resonance imaging were selected. Data was accrued retrospectively from 20092015 and prospectively from 2015 to 2019. Patients were diagnosed with CAA according to Boston criteria. The pattern of distribution of microhemorrhages, changes in white matter and cognitive abilities of patients with and without cerebellar involvement were analyzed. Results. Out of a total of 718 patients, 189 (26.3%) were examined by brain MRI. Of the 189 patients, 155 met the Boston criteria for the diagnosis of cerebral amyloid angiopathy. Patients with CAA and cerebellar involvement were younger (67 + -6 years vs 72 + -10 years, p < 0.001), and have more microhemorrhages 33 + -23 vs 3 + -9, p < 0.001. Patients with cerebellar involvement had a more white matter hyperintensities according to the Fazekas scale. In addition, cognitive disorders are more prevalent in patients with cerebellar involvement, 26% versus 3.6%, p < 0.001. Conclusion: cerebellar involvement is not uncommon in CAA. Most patients have cerebellar microbleedings, have a more aggressive microvascular pattern, and more prominent cognitive changes

Implicarea cerebelului în angiopatia amiloidă cerebrală

Introduction. Cerebral amyloid angiopathy (CAA) is characterized by deposits of beta amyloid in small and medium-sized vessels of the brain and leptomeninges. Lobar hemorrhage is a primary clinical sign of CAA. A subset of hemorrhages located in the cerebellum are thought to be associated with amyloid storage. Aim of the study. Analysis of the involvement of the cerebellum in CAA. Materials and methods. Patients with spontaneous intracerebral hemorrhage that were investigated by magnetic resonance imaging were selected. Data was accrued retrospectively from 2009- 2015 and prospectively from 2015 to 2019. Patients were diagnosed with CAA according to Boston criteria. The pattern of distribution of microhemorrhages, changes in white matter and cognitive abilities of patients with and without cerebellar involvement were analyzed. Results. Out of a total of 718 patients, 189 (26.3%) were examined by brain MRI. Of the 189 patients, 155 met the Boston criteria for the diagnosis of cerebral amyloid angiopathy. Patients with CAA and cerebellar involvement were younger (67 + -6 years vs 72 + -10 years, p < 0.001), and have more microhemorrhages 33 + -23 vs 3 + -9, p < 0.001. Patients with cerebellar involvement had a more white matter hyperintensities according to the Fazekas scale. In addition, cognitive disorders are more prevalent in patients with cerebellar involvement, 26% versus 3.6%, p < 0.001. Conclusion: cerebellar involvement is not uncommon in CAA. Most patients have cerebellar microbleedings, have a more aggressive microvascular pattern, and more prominent cognitive changes.Introducere: Angiopatia amiloidă cerebrală (AAC) este caracterizată prin depozite de amiloid beta în vasele creierului și leptomeningelui. Hemoragia intracerebrală (HI) lobară este semnul clinic al angiopatiei amiloide. Se presupune că un subgrup de hemoragii localizate în cerebel sunt asociate cu AAC. Scopul lucrării: Analiza implicării cerebelului în angiopatia amiloidă cerebrală. Materiale și metode: Au fost selectați pacienții cu hemoragie intracerebrală spontane investigați imagistic prin rezonanță magnetică. Au fost analizați retrospectiv pacienții internați în perioada 2009- 2015 și prospectiv în perioada 2015-2019. Pacienții au fost diagnosticați cu AAC conform criteriilor Boston. Au fost analizate pattern-ul distribuției microhemoragiilor, modificările substanței albe și capacitățile cognitive ale pacienților cu și fără implicarea cerebelului. Rezultate: Din totalul de 718 pacienți, 189 (26,3%) au fost examinați prin IRM cerebrală. Doar 155 pacienți au îndeplinit criteriile Boston pentru diagnosticul de AAC. Pacienții cu AAC și implicarea cerebelului sunt mai tineri (67 +-6 ani vs 72+-10 ani, p < 0.001), și au mai multe microhemoragii comparativ cu pacienții cu ACC fără implicarea cerebelului, 33+-23 vs. 3+-9, p < 0.001. La pacienții cu implicarea cerebelului s-a înregistrat un grad mai sever de afectare a substanței albe conform scalei Fazekas, și o prevalență mai mare a dereglărilor cognitive, 26% versus 3.6%, p < 0.001. Concluzie: implicarea cerebelară nu este rară în AAC. Majoritatea pacienților prezintă microhemoragii cerebelare și hemoragii multiple, au un pattern microvascular mai agresiv, cu dereglările cognitive sunt mai proeminente

Patternul modificărilor substanței albe la pacienții cu angiopatie amiloidă și implicarea cerebelului

Background. Pathological changes in the cerebral white matter can be determined both in small vessel disease and in cerebral amyloid angiopathy. The pattern of involvement may be different depending on the etiology and severity of the process. Objective of the study. Determination and analysis of the pattern of cerebral white matter changes in patients with amyloid angiopathy and involvement of the cerebellum. Material and Methods. Patients with intracerebral hemorrhages who were examined by magnetic resonance imaging were prospectively analyzed. Patients were diagnosed with cerebral amyloid angiopathy (CAA) according to Boston criteria. Changes in white matter were interpreted using the Fazekas scale and compared for patients with CAA and patients with CAA and cerebellar involvement. Results. Of the 614 patients with intracerebral hemorrhage, 96 were examined by cerebral magnetic resonance imaging. Of these, 41 patients were diagnosed with amyloid angiopathy, 19 patients with possible amyloid angiopathy, 21 patients - probable and 1 case with defined amyloid angiopathy. Cerebellar involvement was determined in 34% (14/41) cases. Severe changes in white matter (Fazekas 2-3) were seen patients with cerebellar involvement (12/14; 86% versus 8/27 and 30% p = 0.002). Conclusion. Involvement of the white matter in the pathological process is more significant in patients with amyloid angiopathy and the involvement of the cerebellum, even after adjusting for risk factors. Patients with cerebellar haemorrhage and severe white matter should be screened for amyloid angiopathy. Introducere. Modificări patologice la nivelul substanței albe cerebrale pot fi determinate atât în boala vaselor mici, cât și în angiopatia amiloidă cerebrală. Patternul de implicare poate fi diferit, în dependență de etiologie și gravitatea procesului. Scopul lucrării. Determinarea și analiza patternului modificărilor substanței albe cerebrale la pacienții cu angiopatie amiloidă și implicarea cerebelului. Material și Metode. Au fost analizați prospectiv pacienții cu hemoragii intracerebrale, care au fost examinați prin imagistică și prin rezonanță magnetică. Pacienții au fost diagnosticați cu angiopatie amiloidă cerebrală (AAC) conform criteriilor Boston. Modificările în substanța albă au fost interpretate utilizând scala Fazekas și au fost comparate pentru pacienții cu ACC și pacienții cu AAC și implicarea cerebelului. Rezultate. Din 614 pacienți cu hemoragie intracerebrală, 96 au fost examinați prin rezonanță magnetică cerebrală. Dintre ei, 41 de pacienți au fost diagnosticați cu angiopatie amiloidă, 19 pacienți cu angiopatie amiloidă posibilă, 21 pacienți – probabilă și 1 caz cu angiopatie amiloidă definită. Implicarea cerebelului a fost determinată în 34% (14/41) cazuri. Modificări severe ale substanței albe (Fazekas 2-3) au fost determinate în grupul pacienților cu implicarea cerebelului (12/14; 86% versus 8/27ș 30% p=0.002). Concluzii. Implicarea substanței albe în procesul patologic este mai semnificativă la pacienții cu angiopatie amiloidă și implicarea cerebelului, chiar după ajustarea factorilor de risc. Pacienții cu hemoragie cerebeloasă și patologie severă a substanței albe trebuie examinați pentru angiopatie amiloidă

Актуальность церебральной амилоидной ангиопатии

Update on Amyloid angiopathyAngiopatia amiloidă cerebrală (AAC) este caracterizată prin depozitarea de amiloid beta &icirc;n vasele de calibru mare şi mediu ale creierului şi leptomeningelui. Deşi, deseori asimptomatică, AAC este o cauză importantă a hemoragiei intracerebrale lobare primare la pacienţii v&acirc;rstnici. Poate apărea sporadic, alteori &icirc;n asociere cu boala Alzheimer, sau un alt sindrom familial. Pe l&acirc;ngă hemoragia intracerebrală, ACC se mai poate manifesta cu simptome neurologice tranzitorii, leucoencefalită inflamatorie, poate contribui la dezvoltarea dereglărilor cognitive, sau la depistarea incidentală a microhemoragiilor şi hemosiderozei la examinare prin rezonanţă magnetică. Managementul hemoragiilor cauzate de AAC este similar cu cel din alte hemoragii intracerebrale spontane. Hemoragiile intracerebrale &icirc;n amiloidoza cerebrală au o tendinţă mai mare de recurenţă. Din motiv că antiagregantele şi anticoagulantele cresc frecvenţa şi severitatea hemoragiilor, utilizarea acestor grupuri de medicamente este limitată la pacienţii cu angiopatie amiloidă cerebralăАктуальность церебральной амилоидной ангиопати

White matter hyper-intensity patterns in patients with amyloid angiopathy and cerebellum involvement

Department of Neurology No 1, Department of Neurology No 2 Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: Pathological changes in the cerebral white matter can be determined both in small vessel disease and in cerebral amyloid angiopathy. The pattern of involvement may be different depending on the etiology and severity of the process. Objective of the study: Determination and analysis of the pattern of cerebral white matter changes in patients with amyloid angiopathy and involvement of the cerebellum. Material and methods: Patients with intracerebral hemorrhages who were examined by magnetic resonance imaging were prospectively analyzed. Patients were diagnosed with cerebral amyloid angiopathy (CAA) according to Boston criteria. Changes in white matter were interpreted using the Fazekas scale and compared for patients with CAA and patients with CAA and cerebellar involvement. Of the 614 patients with intracerebral hemorrhage, 96 were examined by cerebral magnetic resonance imaging. Of these, 41 patients were diagnosed with amyloid angiopathy, 19 patients with possible amyloid angiopathy, 21 patients – probable and 1 case with defined amyloid angiopathy. Results: Cerebellar involvement was determined in 34% (14/41) of cases. Severe changes in white matter (Fazekas 2-3) were seen in patients with cerebellar involvement (12/14; 86% versus 8/27 and 30% p = 0.002). Conclusions: Involvement of the white matter in the pathological process is more significant in patients with amyloid angiopathy and the involvement of the cerebellum, even after adjusting for risk factors. Patients with cerebellar haemorrhage and severe white matter should be screened for amyloid angiopathy

Visualization of both proximal M2-MCA segments in patients (the Tilted-V Sign) with acute M1-MCA occlusion stroke is associated with better procedural and prognostic outcomes

IntroductionWe aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments [“Tilted-V sign” (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT).MethodsData for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis.ResultsA total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0–2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0–2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7–8.3).ConclusionTilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality

Safety and effectiveness of IV Thrombolysis in retinal artery occlusion: A multicenter retrospective cohort study.

BACKGROUND Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. METHODS From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA. RESULTS We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group. CONCLUSION Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO

Safety and effectiveness of IV Thrombolysis in retinal artery occlusion: A multicenter retrospective cohort study

Background: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. Methods: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA. Results: We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group. Conclusion: Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO

Reducing the global burden of cerebral venous thrombosis:An international research agenda

Background:Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized.Aims:This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding.Summary of review:This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion.Conclusions:This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements