An Unusual Case of Cerebral Oedema

Neri, Sergio; Giardino, Francesco Ruben; Rizzotto, Agostino

doi:10.12890/2014_000092

Cited by 7 publications

(8 citation statements)

References 5 publications

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“…However, the neurovascular system affected by C1INH impairment was never examined and brain pathology was not evaluated in this knockout mouse model. It is important to note that migraines, stroke, cerebral symptoms, blindness, tetraspasticity, and other irreversible brain damage can also occur in HAE (Bonnaud et al, 2012;Bork et al, 2017;Chung & Kim, 2012;Lasek-Bal, Holecki, Handzlik-Orlik, Smertka, & Dulawa, 2015;Neri et al, 2014). Moreover, HAE patients sometimes manifest with depression and anxiety (Fouche, Saunders, & Craig, 2014).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits

Farfara

Feierman

Richards

et al. 2019

Glia

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The cross‐talk between blood proteins, immune cells, and brain function involves complex mechanisms. Plasma protein C1 inhibitor (C1INH) is an inhibitor of vascular inflammation that is induced by activation of the kallikrein‐kinin system (KKS) and the complement system. Knockout of C1INH was previously correlated with peripheral vascular permeability via the bradykinin pathway, yet there was no evidence of its correlation with blood–brain barrier (BBB) integrity and brain function. In order to understand the effect of plasma C1INH on brain pathology via the vascular system, we knocked down circulating C1INH in wild‐type (WT) mice using an antisense oligonucleotide (ASO), without affecting C1INH expression in peripheral immune cells or the brain, and examined brain pathology. Long‐term elimination of endogenous C1INH in the plasma induced the activation of the KKS and peritoneal macrophages but did not activate the complement system. Bradykinin pathway proteins were elevated in the periphery and the brain, resulting in hypotension. BBB permeability, extravasation of plasma proteins into the brain parenchyma, activation of glial cells, and elevation of pro‐inflammatory response mediators were detected. Furthermore, infiltrating innate immune cells were observed entering the brain through the lateral ventricle walls and the neurovascular unit. Mice showed normal locomotion function, yet cognition was impaired and depressive‐like behavior was evident. In conclusion, our results highlight the important role of regulated plasma C1INH as it acts as a gatekeeper to the brain via the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.

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Section: Discussionmentioning

confidence: 99%

Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits

Farfara

Feierman

Richards

et al. 2019

Glia

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“…A 80 year old study by Crowe and co-workers linked allergy with cerebral oedema, also called cerebral allergic oedema (Crowe, 1942). Another study by Giardino and co-workers demonstrated the presence of cerebral oedema in a 52-year-old patient affected with hereditary angioedema (Giardino et al, 2014). Additionally, Tan and colleagues demonstrated the first incidence of vasogenic cerebral oedema induced by a cell-mediated hypersensitivity reaction to a nickelcontaining aneurysm clip (Tan et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic anti‐amyloid β antibodies cause neuronal disturbances

Adhikari

Khan

Mikhael

et al. 2022

Alzheimer's & Dementia

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Recent published clinical trial safety data showed that 41% of Alzheimer patients experienced amyloid-related imaging abnormalities (ARIA), marks of microhemorrhages and oedema in the brain, following administration of Biogen's Aduhelm/ aducanumab (amino acids 3-7 of the Aβ peptide). Similarly, Janssen/Pfizer's Bapineuzumab (amino acids 1-5 of the Aβ peptide) and Roche's Gantenerumab (amino acids 2-11/18-27 of the Aβ peptide) also displayed ARIA in clinical trials, including microhemorrhage and focal areas of inflammation or vasogenic oedema respectively. The molecular mechanisms underlying ARIA caused by therapeutic anti-Aβ antibodies remain largely unknown, however, recent reports demonstrated that therapeutic antiprion antibodies activate both neuronal apoptotic and allergenic proteomes following cross-linking cellular prion protein. Here, we report that treatment of human induced pluripotent stem cellsderived neurons (HSCN) from a non-demented donor, co-cultured with human primary microglia with anti-Aβ1-6, or anti-Aβ17-23 antibodies activate a significant number of both apoptotic and allergenic-related proteins as assessed by mass spectrometry. Interestingly, a large proportion of the identified proteins included cytokines such as IL-4, IL-12, and IL-13 suggesting a type-1 hypersensitivity response. Following flow cytometry analysis, several proinflammatory cytokines were significantly elevated following anti-Aβ1-6, or anti-Aβ17-23 antibody treatment. These results justify further and more robust investigation of the molecular mechanisms of ARIA during immunotherapy study trials of AD.

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“…However, for patients who have increasing edema unresponsive to steroids, there are few additional medical therapies available. is, combined with recent research that supports bradykinin's role in both tumor invasion and vasogenic edema, has led to interest in the usefulness of C1INH as a potential therapy to decrease the amount of bradykinin generated by malignant glioblastoma cells [3,4,11]. Our case discusses a patient with advanced glioblastoma who had diffuse angioedema refractory to steroid therapy who responded well to plasma-derived C1INH replacement.…”

Section: Introductionmentioning

confidence: 91%

“…e patient at this time also had significantly increased vasogenic cerebral edema seen on imaging on 2/27/2018. Despite these normal labs, it was decided to try plasma-derived C1INH due to literature suggesting potential benefits to cutaneous angioedema, cerebral vasogenic edema, and possible slowing of GBM progression [3,4,11]. e patient was thus started on 20 units/kg infusions twice weekly on 3/13/2018.…”

Section: Case Reportmentioning

confidence: 99%

The Role of C1-Esterase Inhibitors in the Management of Vasogenic Edema in Glioblastoma

Naro

Noverati

Craig

2020

Case Reports in Medicine

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Glioblastoma (GB) is one of the most common adult primary brain tumors, classified as a grade IV astrocytoma and highly malignant in nature. As the tumor grows and disrupts the blood-brain barrier (BBB), vasogenic edema can result. The edema has the potential to significantly contribute to a patient’s morbidity and mortality. Bradykinin has been theorized to play a role in this process as well as encourage tumor spread. Here we discuss a case in which a patient with vasogenic edema and angioedema refractory to antihistamines and high dose corticosteroids responded to C1-esterase inhibitor (C1INH) therapy. Though data exist concerning the role of bradykinin in GB, no clinical studies using C1INH have been done in humans with GB.

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An Unusual Case of Cerebral Oedema

Cited by 7 publications

References 5 publications

Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits

Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits

Therapeutic anti‐amyloid β antibodies cause neuronal disturbances

The Role of C1-Esterase Inhibitors in the Management of Vasogenic Edema in Glioblastoma

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