Identifying diagnostic and prognostic factors in cerebral amyloid angiopathy-related inflammation: A systematic analysis of published and seven new cases.

AIMS: Cerebral amyloid angiopathy (CAA)-related inflammation (CAA-RI) is a potentially reversible manifestation of CAA, histopathologically characterised by transmural and/or perivascular inflammatory infiltrates. We aimed to identify clinical, radiological and laboratory variables capable of improving or supporting the diagnosis of or predicting/influencing the prognosis of CAA-RI and to retrospectively evaluate different therapeutic approaches. METHODS: We present clinical and neuroradiological observations in seven unpublished CAA-RI cases, including neuropathological findings in two definite cases. These cases were included in a systematic analysis of probable/definite CAA-RI cases published in the literature up to 31 December 2021. Descriptive and associative analyses were performed, including a set of clinical, radiological and laboratory variables to predict short-term, 6-month and 1-year outcomes and mortality, first on definite and second on an expanded probable/definite CAA-RI cohort. RESULTS: Data on 205 definite and 100 probable cases were analysed. CAA-RI had a younger symptomatic onset than non-inflammatory CAA, without sex preference. Transmural histology was more likely to be associated with the co-localisation of microbleeds with confluent white matter hyperintensities on magnetic resonance imaging (MRI). Incorporating leptomeningeal enhancement and/or sulcal non-nulling on fluid-attenuated inversion recovery (FLAIR) enhanced the sensitivity of the criteria. Cerebrospinal fluid pleocytosis was associated with a decreased probability of clinical improvement and longer term positive outcomes. Future lobar haemorrhage was associated with adverse outcomes, including mortality. Immunosuppression was associated with short-term improvement, with less clear effects on long-term outcomes. The superiority of high-dose over low-dose corticosteroids was not established. CONCLUSIONS: This is the largest retrospective associative analysis of published CAA-RI cases and the first to include an expanded probable/definite cohort to identify diagnostic/prognostic markers. We propose points for further crystallisation of the criteria and directions for future prospective studies.

Correction to: Predictors of localization, outcome, and etiology of spontaneous intracerebral hemorrhages: focus on cerebral amyloid angiopathy.

The original version of this article unfortunately contained a mistake.

Predictors of localization, outcome, and etiology of spontaneous intracerebral hemorrhages: focus on cerebral amyloid angiopathy.

Despite its clinical relevance, cerebral amyloid angiopathy (CAA) is underdiagnosed worldwide. This retrospective study aimed to assess the incidence, etiology, predictors, and outcome of intracerebral hemorrhages (ICHs) in this region, with special focus on possible underlying CAA. Database screening of acute cares with intracranial hemorrhage diagnosis within 01/07/2014-01/07/2018 were conducted analyzing medical records and imaging. Spontaneous ICHs were classified as deep (basal ganglionic/thalamic/brainstem) and lobar/cerebellar (i.e., CAA-compatible) ICHs. Probable/definite CAA was established using the modified Boston criteria in a subgroup with 'complete' radiological/neuropathological work-up. The ability of several factors to discriminate between deep and lobar/cerebellar ICHs, between probable/definite CAA and non-probable CAA cases, and to predict 1-month case fatality was assessed. Of the 213 ICHs identified, 121 were in deep and 92 in lobar/cerebellar localization. Sub-analysis of 47 lobar/cerebellar ICHs with 'complete' work-up identified 16 probable/definite CAA patients, yielding an estimated 14.7% prevalence of CAA-related ICHs. Chronic hypertension was the most prevalent risk factor for all types of ICHs (including CAA-related), with hypertensive excess and younger age being independent predictors of deep whereas antiplatelet use of lobar/cerebellar localization. The 1-month case fatality was 33.8%, driven predominantly by age and INR > 1.4. Probable/definite CAA diagnosis was independently predicted by age, prior intracranial hemorrhage, and antiplatelet use. First in this region and among the few in the literature, this study reports a remarkable prevalence of CAA-related ICHs, emphasizing the need for an increased awareness of CAA and its therapeutic implications, especially regarding antiplatelets among the elderly.

[Evaluation of resection margins following breast conserving surgery for breast cancer. A multicentric retrospective study]. / Emlorák miatti szervmegtartó mutétek reszekciós széleinek vizsgálata. Multicentrikus retrospektív elemzés.

Introduction: Breast conserving surgery for breast cancer requires the analysis of surgical margins. If the tumor is not removed completely, additional treatments (reoperation, boost irradiation) are generally recommended. Aim: To analyze the information content of histopathology reports on surgical margins in consecutive cases of breast conservation for invasive female breast cancer, to evaluate the frequency of incompletely removed tumors and to estimate the rate of further treatments after incomplete removal. Method: Analysis of margin related data of consecutive histopathology reports from 8 Hungarian pathology units with locoregional treatment related data in case of unsafe margins. Results: 386 reports were analyzed after exclusions. 200 and 32 cases were identified as having unsafe margins according to the previous (<5 mm) and the new (0 mm) definition of unclear margin, respectively. Unsafe margins were more common with lobular carcinomas. Specimens with clear margins weighed more. Reoperations for unsafe margins were performed in 43/180 and 12/22 cases according to the previous and the new definitions, respectively. Only 75/137 patients without reoperation received boost irradiation of the tumor bed; information on boost radiotherapy was often missing. Residual cancer was identified in 15/43 reoperated patients, of whom 9 had >0 mm margin distance. Conclusions: Some pathology reports lack information on surgical margins. Unsafe margin rates decreased with the new definition. Residual cancer may be left behind in case of clear margins with no ink on tumor. Neither reoperation, nor boost radiotherapy is given to some patients with unclear surgical margins. Orv Hetil. 2019; 160(26): 1036-1044.

Exploiting the Therapeutic Potential of Endogenous Immunomodulatory Systems in Multiple Sclerosis-Special Focus on the Peroxisome Proliferator-Activated Receptors (PPARs) and the Kynurenines.

Multiple sclerosis (MS) is a progressive neurodegenerative disease, characterized by autoimmune central nervous system (CNS) demyelination attributable to a disturbed balance between encephalitic T helper 1 (Th1) and T helper 17 (Th17) and immunomodulatory regulatory T cell (Treg) and T helper 2 (Th2) cells, and an alternatively activated macrophage (M2) excess. Endogenous molecular systems regulating these inflammatory processes have recently been investigated to identify molecules that can potentially influence the course of the disease. These include the peroxisome proliferator-activated receptors (PPARs), PPARγ coactivator-1alpha (PGC-1α), and kynurenine pathway metabolites. Although all PPARs ameliorate experimental autoimmune encephalomyelitis (EAE), recent evidence suggests that PPARα, PPARß/δ agonists have less pronounced immunomodulatory effects and, along with PGC-1α, are not biomarkers of neuroinflammation in contrast to PPARγ. Small clinical trials with PPARγ agonists have been published with positive results. Proposed as immunomodulatory and neuroprotective, the therapeutic use of PGC-1α activation needs to be assessed in EAE/MS. The activation of indolamine 2,3-dioxygenase (IDO), the rate-limiting step of the kynurenine pathway of tryptophan (Trp) metabolism, plays crucial immunomodulatory roles. Indeed, Trp metabolites have therapeutic relevance in EAE and drugs with structural analogy to kynurenines, such as teriflunomide, are already approved for MS. Further studies are required to gain deeper knowledge of such endogenous immunomodulatory pathways with potential therapeutic implications in MS.