Brain MRI findings in children and adolescents with Fabry disease

Marchesoni, Cintia; Cisneros, Ernesto Bernal; Pfister, Pablo Martin; Yañez, Paulina; Rollán, Cecilia; Romero, Carlos; Kisinovsky, Isaac; Rattagan, L.; Cejas, Luciana León; Pardal, Ana; Sevlever, Gustavo; Reisin, Ricardo

doi:10.1016/j.jns.2018.10.009

Cited by 15 publications

(19 citation statements)

References 49 publications

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“…Cerebral ischemia-reperfusion is a complicated pathological process. The damage and cascade of reactions caused by ischemia and reperfusion in brain tissues are related to decreased blood flow, ischemic-induced energy metabolism disorder, oxidative stress, inflammatory stress, cytokine damage, excitatory toxicity by glutamate, intracellular calcium overload, NO synthesis, and many other factors [2,3,4,5,6,7,100], even including some genetic disease as a possible complication, such as Fabry disease [100,101]. Moreover, the numerous abovementioned factors and mechanisms that lead to CI/RI are related to each other and can interact with and cause each other, eventually leading to apoptosis or nerve necrosis in the ischemic region [102,103].…”

Section: Conclusion and Remarksmentioning

confidence: 99%

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

Xie

Zhou

Sun

et al. 2018

Cells

136

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Cerebral ischemia-reperfusion is a complicated pathological process. The injury and cascade reactions caused by cerebral ischemia and reperfusion are characterized by high mortality, high recurrence, and high disability. However, only a limited number of antithrombotic drugs, such as recombinant tissue plasminogen activator (r-TPA), aspirin, and heparin, are currently available for ischemic stroke, and its safety concerns is inevitable which associated with reperfusion injury and hemorrhage. Therefore, it is necessary to further explore and examine some potential neuroprotective agents with treatment for cerebral ischemia and reperfusion injury to reduce safety concerns caused by antithrombotic drugs in ischemic stroke. Ginseng Rg1 (G-Rg1) is a saponin composed of natural active ingredients and derived from the roots or stems of Panax notoginseng and ginseng in traditional Chinese medicine. Its pharmacological effects exert remarkable neurotrophic and neuroprotective effects in the central nervous system. To explore and summarize the protective effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury, we conducted this review, in which we searched the PubMed database to obtain and organize studies concerning the pharmacological effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury. This study provides a valuable reference and clues for the development of new agents to combat ischemic stroke. Our summarized review and analysis show that the pharmacological effects of and mechanisms underlying ginsenoside Rg1 activity against cerebral ischemia and reperfusion injury mainly involve 4 sets of mechanisms: anti-oxidant activity and associated apoptosis via the Akt, Nrf2/HO-1, PPARγ/HO-1, extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK) pathways (or mitochondrial apoptosis pathway) and the caspase-3/ROCK1/MLC pathway; anti-inflammatory and immune stimulatory-related activities that involve apoptosis or necrosis via MAPK pathways (the JNK1/2 + ERK1/2 and PPARγ/HO-1 pathways), endoplasmic reticulum stress (ERS), high mobility group protein1 (HMGB1)-induced TLR2/4/9 and receptor for advanced glycation end products (RAGE) pathways, and the activation of NF-κB; neurological cell cycle, proliferation, differentiation, and regeneration via the MAPK pathways (JNK1/2 + ERK1/2, PI3K-Akt/mTOR, PKB/Akt and HIF-1α/VEGF pathways); and energy metabolism and the regulation of cellular ATP levels, the blood-brain barrier and other effects via N-methyl-D-aspartic acid (NMDA) receptors, ERS, and AMP/AMPK-GLUT pathways. Collectively, these mechanisms result in significant neuroprotective effects against cerebral ischemic injury. These findings will be valuable in that they should further promote the development of candidate drugs and provide more information to support the application of previous findings in stroke clinical trials.

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Section: Conclusion and Remarksmentioning

confidence: 99%

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

Xie

Zhou

Sun

et al. 2018

Cells

136

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“…White matter lesions (WMLs) – ie, localized hyperintensities on brain magnetic resonance imaging T2-weighted and fluid-attenuated inversion-recovery sequences, which are considered a surrogate marker of cerebral small vessel disease84 – are present in almost half of the patients with FD, and their prevalence increases with age,69,85 with classically affected men exhibiting the highest risk 69. Since asymptomatic WMLs have been identified in school-age children and adolescents with classic FD,86 the natural history of FD-related brain microvascular disease may start early in life and follow a protracted, asymptomatic course for many years. The AGAL activity measured in classically affected males is typically null or severely reduced, but patients with REA <1% have considerably faster CKD progression rates than patients with higher REA levels 32…”

Section: Clinical Phenotypes and Their Pathology Correlatesmentioning

confidence: 99%

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>

Oliveira¹,

Ferreira²

2019

TACG

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Fabry disease (FD) is a rare X-linked glycosphingolipidosis resulting from deficient α-galactosidase A (AGAL) activity, caused by pathogenic mutations in the GLA gene. In males, the multisystemic involvement and the severity of tissue injury are critically dependent on the level of AGAL residual enzyme activity (REA) and on the metabolic load of the disease, but organ susceptibility to damage varies widely, with heart appearing as the most vulnerable to storage pathology, even with relatively high REA. The expression of FD can be conceived as a multidomain phenotype, where each of the component domains is the laboratory or clinical expression of the causative GLA mutation along a complex pathophysiologic cascade pathway. The AGAL enzyme activity is the most clinically useful marker of the protein phenotype. The metabolic phenotype and the pathologic phenotype are diverse expressions of the storage pathology, respectively, assessed by biochemical and histological/ultrastructural methods. The storage phenotypes are the direct consequences of enzyme deficiency and hence, together with the enzymatic phenotype, constitute the more specific diagnostic markers of FD. In the pathophysiology cascade, the clinical phenotypes are most distantly linked to the underlying genetic causation, being critically influenced by the patients' gender and age, and modulated by the effects of variation in other genetic loci, of polygenic inheritance and of environmental risk factors. A major challenge in the clinical phenotyping of patients with FD is the differential diagnosis between its nonspecific, later-onset complications, particularly the cerebrovascular, cardiac and renal, and similar chronic illnesses that are common in the general population. Comprehensive phenotyping, whenever possible performed in hemizygous males, is therefore crucial for grading the severity of pathogenic GLA variants, to clarify the phenotypic correlations of hypomorphic alleles, to define benign polymorphisms, as well as to establish the pathogenicity of variants of uncertain significance.

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“…Furthermore, 50% of males and 38% of females suffered their stroke before the diagnosis of FD was made [2] . Moreover, FD has been identified as an under diagnosed etiology of stroke in the young [3] , [4] , [5] Among patients with FD and no history of stroke or transient ischemic attack (TIA), 44% of adults and 15.9% of adolescents had silent brain infarcts on brain magnetic resonance imaging (MRI) [6] , [7] .…”

Section: Introductionmentioning

confidence: 99%

Fabry disease patients have an increased risk of stroke in the COVID-19 ERA. A hypothesis

2020

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Stroke is a severe and frequent complication of Fabry disease (FD), affecting both males and females. Cerebrovascular complications are the end result of multiple and complex pathophysiology mechanisms involving endothelial dysfunction and activation, development of chronic inflammatory cascades leading to a prothrombotic state in addition to cardioembolic stroke due to cardiomyopathy and arrhythmias. The recent coronavirus disease 2019 outbreak share many overlapping deleterious pathogenic mechanisms with those of FD and therefore we analyze the available information regarding the pathophysiology mechanisms of both disorders and hypothesize that there is a markedly increased risk of ischemic and hemorrhagic cerebrovascular complications in Fabry patients suffering from concomitant SARS-CoV-2 infections.

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Brain MRI findings in children and adolescents with Fabry disease

Cited by 15 publications

References 49 publications

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>

Fabry disease patients have an increased risk of stroke in the COVID-19 ERA. A hypothesis

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Brain MRI findings in children and adolescents with Fabry disease

Cited by 15 publications

References 49 publications

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype&ndash;phenotype correlations</p>

Fabry disease patients have an increased risk of stroke in the COVID-19 ERA. A hypothesis

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<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>