Thrombosis of Developmental Venous Anomalies of the Brain After Liver Transplantation

AbstractCerebral cavernous malformations (CCM) are a neurovascular anomaly that may occur sporadically in otherwise healthy individuals, or be inherited by autosomal dominant mutations in the genes that encode the proteins of the CCM signaling complex (KRIT1, CCM2, or PDCD10)1–4. CCMs have long been known to follow a genetic two-hit model where lesion formation is initiated by somatic mutations resulting in biallelic loss of a CCM complex gene5–8. Recent studies have shown that somatic mutations in MAP3K3 and PIK3CA also contribute to CCM pathogenesis9–11; however, it remains unclear how these mutations contribute to sporadic versus familial cases. Here we show that somatic mutations in MAP3K3 are mutually exclusive with mutations in CCM complex genes and that mutations in MAP3K3 contribute to sporadic, but not familial CCM. Using single-nucleus DNA sequencing, we show that co-occurring MAP3K3 and PIK3CA mutations are present within the same clonal population of cells. Furthermore, we identify PIK3CA mutations in CCM-associated developmental venous anomalies (DVA). It has long been known that sporadic CCM often develop in the vicinity of a DVA. However, the underlying cause of this association is unknown12–14. In this first report of the molecular pathology of CCM-associated DVA, we find that the identical PIKC3A mutation is found in both the DVA and its associated CCM, but that an activating MAP3K3 mutation appears only in the CCM. These results support a mechanism where DVA develop as the result of a PIK3CA mutation, creating a region of the brain vasculature that functions as a genetic primer for CCM development following acquisition of an additional somatic mutation.

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A review of extraaxial developmental venous anomalies of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, venous varices or aneurysmal malformations, and enlarged emissary veins

Neurosurgical FOCUS ◽

10.3171/2018.5.focus18107 ◽

2018 ◽

Vol 45 (1) ◽

pp. E9 ◽

Cited By ~ 11

Author(s):

Sunil Manjila ◽

Timothy Bazil ◽

Matthew Thomas ◽

Sunithi Mani ◽

Matthew Kay ◽

...

Keyword(s):

Natural History ◽

Venous Hypertension ◽

Venous Flow ◽

Sinus Pericranii ◽

Venous Anomalies ◽

Broad Concept ◽

Emissary Veins ◽

Developmental Venous Anomalies ◽

The Brain

This paper is a narrative review of extraaxial developmental venous anomalies (eDVAs) of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, enlarged emissary veins, and venous varices or aneurysmal malformations. The article highlights the natural history, anatomy, embryology, imaging, clinical implications, and neurosurgical significance of these lesions, which the authors believe represent a continuum, with different entities characterized by distinct embryopathologic features. The indications and surgical management options are discussed for these individual intracranial pathologies with relevant illustrations, and a novel classification is proposed for persistent falcine sinus (PFS). The role of neurointervention and/or microsurgery in specific cases such as sinus pericranii and enlarged emissary veins of the skull is highlighted.A better understanding of the pathophysiology and developmental anatomy of these lesions can reduce treatment morbidity and mortality. Some patients, including those with vein of Galen malformations (VOGMs), can present with the added systemic morbidity of a high-output cardiac failure. Although VOGM is the most studied and classified of the above-mentioned eDVAs, the authors believe that grouping the former with the other venous anomalies/abnormalities listed above would enable the clinician to convey the exact morphophysiological configuration of these lesions, predict their natural history with respect to evolving venous hypertension or stroke, and extrapolate invaluable insights from VOGM treatment to the treatment of other eDVAs. In recent years, many of these symptomatic venous malformations have been treated with endovascular interventions, although these techniques are still being refined. The authors highlight the broad concept of eDVAs and hope that this work will serve as a basis for future studies investigating the role of evolving focal venous hypertension/global intracranial hypertension and possibilities of fetal surgical intervention in these cases.

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Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

Journal of Child Science ◽

10.1055/s-0041-1731079 ◽

2021 ◽

Vol 11 (01) ◽

pp. e145-e147

Author(s):

Nida Mirza ◽

Ravi Bharadwaj ◽

Smita Malhotra ◽

Anupam Sibal

Keyword(s):

Liver Transplantation ◽

Liver Failure ◽

Acute Liver Failure ◽

Wilson Disease ◽

Prognostic Score ◽

Prognostic Index ◽

Kidney Injury ◽

Copper Metabolism ◽

Life Saving ◽

The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

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