Cyclosporin A-related cerebral vasculopathy

Shbarou, RM; Chao, N.J.; Morgenlander, Joel C.

doi:10.1038/sj.bmt.1702603

Cited by 29 publications

(13 citation statements)

References 7 publications

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“…In our patients with cerebrovascular disease, however, the distribution of infarcts or ICH was different from that in patients with neurotoxicity [13,14,15]. In addition, cyclosporine was already withheld at the onset of attacks in 2 of the 4 patients with cerebrovascular disease due to systemic infection or poor general condition.…”

Section: Discussionmentioning

confidence: 96%

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New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

et al. 2004

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Purpose: To identify the probable etiologies and characteristics of new-onset seizures after orthotopic liver transplantation (OLT) and to assess their clinical implications and prognosis. Methods: We retrospectively analyzed the clinical, electrophysiologic and laboratory data of 17 patients with new-onset seizures after OLT among 367 adult and pediatric patients who underwent OLT between 1999 and 2001. Results: A suspected etiology of seizures was identified in most patients, including 6 (35.2%) with neurotoxicity due to immunosuppressive therapy, 4 (23.5%) with cerebrovascular disease, 3 (17.6%) with severe metabolic derangement by sepsis or rejection, and 1 each (5.8%) with hyperglycemia and brain edema due to fulminant hepatic failure. Causative factors could not be identified in 2 patients (11.8%). Seizures recurred in 15 patients (88.2%), with 9 occurring on the same day as the original seizure. Attacks caused by neurotoxicity tended to have an earlier onset, within 1 week in 4 of 6 patients, than those caused by cerebrovascular disease and sepsis/rejection, but this was not statistically significant. A total of 21 EEGs were performed in 13 patients. Eleven patients had abnormal EEG findings, of whom 4 (30.7%) showed epileptiform discharges, but the outcome of patients with epileptiform activity did not differ statistically from that of patients without such discharges (p > 0.6). The incidence of poor outcome (death or persistent vegetative state) in the group with seizures was almost 10 times higher than in the group without seizures (52.9 vs. 5.7%, p < 0.001). The prognosis of patients with seizures due to cerebrovascular disease and severe metabolic derangement by sepsis/rejection was poorer than that of patients with seizures caused by the neurotoxicity of immunosuppressive drugs (p < 0.02), suggesting that the underlying cause of seizures is important in determining prognosis. Of 8 patients who survived, 1 was lost to follow-up. The long-term outcome of seizures in surviving patients was excellent, with all survivors available for follow-up being seizure-free for a mean follow-up of 42.5 months (range, 16–58 months). Conclusion: New-onset seizures after OLT may herald fatal outcome, especially in patients with cerebrovascular disease or sepsis. The prognosis of seizures in survivors is excellent, and long-term antiepileptic drugs are not required in most cases.

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Section: Discussionmentioning

confidence: 96%

“…In both patients, seizures occurred following administration of these drugs and resolved after their withdrawal. Although the mechanism of neurotoxicity is not completely known, cyclosporine has been reported to cause vasoconstriction and endothelial damage [13,14,15]. …”

Section: Discussionmentioning

confidence: 99%

New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

et al. 2004

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“…27 MRI studies of PRES patients have also revealed characteristics of reversible vasogenic edema congruent with our findings in the present ARE model; hyperintensities are seen in T 2 w MR images along with concomitant increases in the ADC, most prominently in the occipital or occipito-parietal lobes, 5,42 and a narrowing or beaded appearance for the vessels in MRA, reflecting an underlying vasospasm and/or vasoconstriction. 40,41,43 The distribution of lesions in the present ARE model was primarily diffuse, but tended to favor the occipito-parietal area (Bregma À4 to À6 mm). Although it is not clearly identified, both PRES and ARE are likely to be based on the similar pathogenesis (endothelial damage) due to hypertension and CsA.…”

Section: Discussionmentioning

confidence: 99%

Transient increase of fractional anisotropy in reversible vasogenic edema

Kimura-Ohba

Yang

Thompson

et al. 2016

J Cereb Blood Flow Metab

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Brain vasogenic edema, involving disruption of the blood-brain barrier, is a common pathological condition in several neurological diseases, with a heterogeneous prognosis. It is sometimes reversible, as in posterior reversible encephalopathy syndrome, but often irreversible and our current clinical tools are insufficient to reveal its reversibility. Here, we show that increased fractional anisotropy in magnetic resonance imaging is associated with the reversibility of vasogenic edema. Spontaneously, hypertensive rats-stroke prone demonstrated posterior reversible encephalopathy syndrome-like acute encephalopathy in response to high-dose cyclosporine A treatment; the deteriorating neurological symptoms and worsening scores in behavioral tests, which were seen in acute phase, dissappered after recovery by cessation of cyclosporine A. In the acute phase of encephalopathy, the fractional anisotropy and apparent diffusion coefficient increased in areas with IgG leakage. This increase of fractional anisotropy occurred in the absence of demyelination: fluid leakage into the myelinated space increased the axial, but not the radial, diffusivity, resulting in the increased fractional anisotropy. This increased fractional anisotropy returned to pre-encephalopathy values in the recovery phase. Our results highlight the importance of the fractional anisotropy increase as a marker for the reversibility of brain edema, which can delineate the brain areas for which recovery is possible. KeywordsBlood-brain barrier, brain vasogenic edema, diffusion tensor imaging, fractional anisotropy, posterior reversible encephalopathy syndrome

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“…CA and MRA demonstrate focal vasoconstriction, focal vasodilation, string-of-beads appearance, and vessel pruning, undoubtedly reflecting endothelial dysfunction (increased and decreased vessel tone) or reduced flow. 21,24,37,40,46,47,[94][95][96] Diffuse vasoconstriction is also present. 24 These features have been noted in hypertensive as well as nonhypertensive patients and have been shown to reverse.…”

Section: Evidence Of Hypoperfusion In Presmentioning

confidence: 99%

Posterior Reversible Encephalopathy Syndrome, Part 2: Controversies Surrounding Pathophysiology of Vasogenic Edema

Bartynski¹

2008

AJNR Am J Neuroradiol

946

790

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SUMMARY:Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state accompanied by a unique brain imaging pattern typically associated with a number of complex clinical conditions including: preeclampsia/eclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases and high dose cancer chemotherapy. The mechanism behind the developing vasogenic edema and CT or MR imaging appearance of PRES is not known. Two theories have historically been proposed: 1) Severe hypertension leads to failed auto-regulation, subsequent hyperperfusion, with endothelial injury/vasogenic edema and; 2) vasoconstriction and hypoperfusion leads to brain ischemia and subsequent vasogenic edema. The strengths/weaknesses of these hypotheses are reviewed in a translational fashion including supporting evidence and current available imaging/clinical data related to the conditions that develop PRES. While the hypertension/hyperperfusion theory has been most popular, the conditions associated with PRES have a similar immune challenge present and develop a similar state of T-cell/endothelial cell activation that may be the basis of leukocyte trafficking and systemic/cerebral vasoconstriction. These systemic features along with current vascular and perfusion imaging features in PRES appear to render strong support for the older theory of vasoconstriction coupled with hypoperfusion as the mechanism.T he mechanism of posterior reversible encephalopathy syndrome (PRES) is not known. Two opposing hypotheses are commonly cited, but the issue is controversial: 1) The current more popular theory suggests that severe hypertension exceeds the limits of autoregulation, leading to breakthrough brain edema; 2) the earlier original theory suggests that hypertension leads to cerebral autoregulatory vasoconstriction, ischemia, and subsequent brain edema. The issues surrounding these theories are reviewed to summarize the potential values of each mechanism. Current Popular Theory: Hypertension, Failed Autoregulation, HyperperfusionSevere hypertension with failed autoregulation, injury to the capillary bed, and hyperperfusion remains the most popular theory for the brain edema that develops in PRES. [1][2][3][4] This concept is naturally intuitive, due to the frequent presence of hypertension at toxicity, and was originally embraced as the cause of eclampsia, historically labeled as a "hypertensive disorder of pregnancy." The hypertension/hyperperfusion theory is primarily based on blood pressure exceeding the autoregulation limits of the brain. AutoregulationAutoregulation is an intrinsic function of the vasculature of the brain, designed to maintain a stable blood flow in the face of fluctuating blood pressure. 5,6 Under normal circumstances, brain vessels possess intrinsic vascular tone.7 With autoregulation, vasodilation occurs as blood pressure drops and vasoconstriction occurs as blood pressure increases. [5][6][7] This function is regulated by the endothelium with release of relaxing factors (endothelium-de...

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Cyclosporin A-related cerebral vasculopathy

Cited by 29 publications

References 7 publications

New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

Transient increase of fractional anisotropy in reversible vasogenic edema

Posterior Reversible Encephalopathy Syndrome, Part 2: Controversies Surrounding Pathophysiology of Vasogenic Edema

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