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      Clinical Characteristics of Transplant-associated Encephalopathy in Children

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          Abstract

          We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) ( P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) ( P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

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          Cerebral blood flow in patients with chronic heart failure before and after heart transplantation.

          Arterial blood pressure and cardiac output are often reduced in patients with chronic heart failure (CHF). Counterregulatory mechanisms with increased neurohormonal activation and changes in the distribution of cardiac output are assumed to secure vital organ perfusion. However, clinical examination of patients with CHF frequently reveals neurological symptoms with dizziness and memory problems, suggesting altered brain perfusion. In this study we determined whether cerebral blood flow (CBF) is reduced in patients with New York Heart Association (NYHA) functional class III and IV (n=12) compared with healthy control subjects (n=12). Furthermore, we examined whether heart transplantation (n=5) could restore CBF. CBF was estimated by single-photon emission computed tomography and (133)Xe as tracer, and middle cerebral artery velocity was measured by transcranial Doppler ultrasound. In the CHF patients, CBF was 36+/-1 mL/min per 100 g, corresponding to a 31% reduction compared with the control group (52+/-5 mL/min per 100 g) (P<0.05). After heart transplantation, CBF increased from 35+/-3 mL/min per 100 g before transplantation to 50+/-3 mL/min per 100 g within the first postoperative month (P<0.05). We conclude that CBF is substantially, but reversibly, reduced in patients with NYHA class III/IV heart failure. This phenomenon suggests that redistribution of cardiac output inadequately secures brain perfusion in patients with severe CHF.
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            Neurologic complications after solid organ transplantation.

            Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients experiences neurologic alterations with incidence ranging from 10% to 59%. The complications can be divided into such of those common to all types of transplant and others of those specific to transplanted organ. The most common complication seen with all types of transplanted organ is neurotoxicity attributable to immunosuppressive drugs, followed by seizures, opportunistic central nervous system (CNS) infections, cardiovascular events, encephalopathy and de novo CNS neoplasms. Amongst immunosuppressants, calcineurin inhibitors are the main drugs involved in neurotoxicity, leading to complications which ranges from mild symptoms, such as tremors and paresthesia to severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Neurologic complications of liver transplantation are more common than that of other solid organ transplants (13-47%); encephalopathy is the most common CNS complication, followed by seizures; however, central pontine myelinolysis can appear in 1-8% of the patients leading to permanent disabilities or death. In kidney transplanted patients, stroke is the most common neurologic complication, whereas cerebral infarction and bleeding are more typical after heart transplantation. Metabolic, electrolyte and infectious anomalies represent common risk factors; however, identification of specific causes and early diagnosis are still difficult, because of patient's poor clinical status and concomitant systemic and metabolic disorders, which may obscure symptoms.
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              Postischemic Hyperperfusion on Arterial Spin Labeled Perfusion MRI is Linked to Hemorrhagic Transformation in Stroke

              The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                March 2017
                05 January 2017
                : 32
                : 3
                : 457-464
                Affiliations
                [1 ]Department of Pediatrics, Kyungpook National University Hospital, Daegu, Korea.
                [2 ]Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
                [3 ]Department of Pediatrics, CHA Gangnam Medical Center, CHA University, Seoul, Korea.
                Author notes
                Address for Correspondence: Tae-Sung Ko, MD. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. tsko@ 123456amc.seoul.kr

                *Yun-Jeong Lee and Mi-Sun Yum contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-3472-5336
                http://orcid.org/0000-0003-1311-3955
                http://orcid.org/0000-0003-3143-9545
                http://orcid.org/0000-0002-8081-6522
                http://orcid.org/0000-0001-7896-6751
                http://orcid.org/0000-0001-8799-4068
                http://orcid.org/0000-0001-7960-4752
                http://orcid.org/0000-0001-7653-2036
                http://orcid.org/0000-0002-8213-8964
                Article
                10.3346/jkms.2017.32.3.457
                5290105
                28145649
                b214039f-5cae-44ca-a89f-a03c828abc41
                © 2017 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 August 2016
                : 30 October 2016
                Categories
                Original Article
                Pediatrics

                Medicine
                encephalopathy,transplantation,liver,kidney,heart,hematopoietic stem cells
                Medicine
                encephalopathy, transplantation, liver, kidney, heart, hematopoietic stem cells

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