Cyclosporine A-associated fatal central nervous system angiopathy in a bone marrow transplant recipient: an autopsy case

Koide, Takashi; Yamada, Miyuki; Takahashi, Takayuki; Igarashi, Syuichi; Masuko, Masayoshi; Furukawa, Tatsuo; Kobayashi, Takashi; Koike, Terumoto; Sato, Mitsuya; Tanaka, R.; Tsuji, Sachiko; Takahashi, Hitoshi

doi:10.1007/s004010051179

Cited by 16 publications

(6 citation statements)

References 17 publications

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“…Histopathologic evidence of acute and chronic vessel injury has been described in postmortem studies, including intimal thickening, segmental vessel narrowing, intimal dissection, and organized thrombi. 28 This supports a pathologic process similar to that of TMA. Minute hemorrhages as well as focal hematoma and sulcal hemorrhage can be seen with PRES.…”

Section: Discussionsupporting

confidence: 63%

Suspicious Neuroimaging Pattern of Thrombotic Microangiopathy

Ellchuk¹,

Shah²,

Hewlett³

et al. 2011

AJNR Am J Neuroradiol

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SUMMARY:The TMAs are a group of microvascular occlusive disorders characterized by thrombocytopenia and intravascular hemolysis. Literature review reveals a spectrum of neuroimaging findings, including a single case report of multifocal hemorrhagic infarctions. We present a series of 12 patients with TMA demonstrating a similar pattern of multifocal cortical and subcortical hemorrhagic infarctions.ABBREVIATIONS: ADC ϭ apparent diffusion coefficient; AML ϭ acute myelogenous leukemia; CLL ϭ chronic lymphocytic leukemia; CNS ϭ central nervous system; CTV ϭ CT venography; DIC ϭ disseminated intravascular coagulation; DWI ϭ diffusion-weighted imaging; GRE ϭ gradient recalled-echo; HIV ϭ human immunodeficiency virus; HUS ϭ hemolytic uremic syndrome; mHTN ϭ malignant hypertension; MRI ϭ MR imaging; MRV ϭ MR venography; PRES ϭ posterior reversible encephalopathy syndrome; SWI ϭ susceptibility-weighted imaging; TMA ϭ thrombotic microangiopathy; TTP ϭ thrombotic thrombocytopenic purpura; vWF ϭ von Willebrand factor T MA was defined by Symmers in 1952 1 as a lesion of arteriole and capillary wall thickening with swelling or detachment of endothelial cells from the basement membrane, accumulation of material in the subendothelial space, and lodging of fibrin-platelet thrombi at the arteriocapillary junction.2 The mechanical injury to erythrocytes results in intravascular hemolysis and schistocytosis. The intraluminal platelet thrombosis results in partial or complete obstruction of the vessel lumina.

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Section: Discussionsupporting

confidence: 63%

Suspicious Neuroimaging Pattern of Thrombotic Microangiopathy

Ellchuk¹,

Shah²,

Hewlett³

et al. 2011

AJNR Am J Neuroradiol

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“…91 Endothelial injury, including cerebral arterial dissection, was observed in autopsy studies of patients with cyclosporine toxicity. 92 Endothelial injuries in association with activation of cell adhesion molecules and cytokines have been implicated in eclampsia, infection, transplantation, and perhaps other conditions. 68 A damaged endothelium in the cerebral arteries may lead to an impaired autoregulation and, hence, lower the blood pressure threshold for autoregulatory breakthrough.…”

Section: Pres Pathogenesis and Mechanismmentioning

confidence: 99%

Posterior Reversible Encephalopathy Syndrome: Clinicoradiological Spectrum and Therapeutic Strategies

Jenny

Castaldo

2012

Hospital Practice

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Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance, and seizures. In most cases, symptoms present acutely or subacutely in the setting of accelerated hypertension, eclampsia, autoimmune disease, immunosuppressive treatment, or cancer chemotherapy. One essential feature of PRES is the presence of reversible cerebral vasogenic edema that has a predominantly posterior distribution on brain imaging. Atypical imaging features are commonly described, including involvement of the anterior brain or brainstem and the coexistence of ischemia or hemorrhage. In most cases, both clinical and radiological findings are reversible, although permanent imaging abnormalities and residual neurological sequelae can be seen in a minority of patients. The syndrome is thought to be caused by a breakdown of the blood-brain barrier and an extravasation of the intravascular fluid. Treatment of hypertension and seizures, and withdrawal of causative agents are the mainstays of therapy in PRES.

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“…Furthermore, it was shown to cause direct toxic damage to brain cells, particularly to oligodendrocytes and neurons (McDonald et al 1996), as well as mild cerebral cell loss (Nassbaum et al 1995). Several fatal cyclosporin A-associated deaths have been presented in the literature (Nassbaum et al 1995;de Perrot et al 2000;Koide et al 2000), one of them in a medico-legal setting after accidental administration of the drug in a 10-fold concentration via a central line: the patient subsequently developed a massive cerebral oedema with brainstem compression resulting in death (de Perrot et al 2000). The non-accidental cases were also characterised by substantial cerebral oedema resulting in brain stem compression (Nassbaum et al 1995;Koide et al 2000), of which the more recent case showed a unique angiopathy with segmental narrowing of the basilar artery with intimal dissection resulting in multiple necrotic CNS lesions (Koide et al 2000).…”

Section: Discussionmentioning

confidence: 97%

“…Administration of cyclosporin A is known to be associated with a wide range of systemic complications: neurotoxicity is noted in approximately 20% of patients and symptoms such as tremors, paraesthesias, headaches, confusion, seizures and coma have been recorded (Koide et al 2000). The cyclosporin A encephalopathy is usually associated with white matter hypoattenuation on cranial CT scans, but is generally reversible after discontinuation of the drug (Hughes 1990).…”

Section: Discussionmentioning

confidence: 98%

Mycotic cerebral vasculitis in a paediatric cardiac transplant patient excludes misadventure

et al. 2002

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We present the case of a 10-year-old girl with cardiomyopathy who received a heart transplant. Due to organ rejection, the dosage of immunosuppressive agents was increased postoperatively. The patient complained of intermittent headaches in the following days and developed a haemorrhagic necrosis of the left thalamus. A week later, an oral dose of cyclosporin A was accidentally given intravenously, and 2 weeks later a recurrent subarachnoid haemorrhage of unknown origin was diagnosed. The clinical course was then characterised by progressive deterioration resulting in coma, fluctuating brain stem symptoms and the development of a massive cerebral oedema with subsequent brain death. A coroner's autopsy was instigated to investigate a claim of medical misadventure. Neuropathological investigations found a focal infiltration of fungal hyphae in the left posterior cerebral artery resulting in necrosis of the vascular wall and thus explaining the source of the recurrent subarachnoid haemorrhage which eventually resulted in the girl's death. Medical misadventure due to the administration of cyclosporin was not directly responsible for the death of this patient. This case illustrates that it is of paramount importance to copiously sample and investigate the basal cerebral arteries in cases of subarachnoid haemorrhage of unknown origin, in particular in a medico-legal context.

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Cyclosporine A-associated fatal central nervous system angiopathy in a bone marrow transplant recipient: an autopsy case

Cited by 16 publications

References 17 publications

Suspicious Neuroimaging Pattern of Thrombotic Microangiopathy

Suspicious Neuroimaging Pattern of Thrombotic Microangiopathy

Posterior Reversible Encephalopathy Syndrome: Clinicoradiological Spectrum and Therapeutic Strategies

Mycotic cerebral vasculitis in a paediatric cardiac transplant patient excludes misadventure

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