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Dilibe A, Subramanian L, Poyser TA, Oriaifo O, Brady R, Srikanth S, Adabale O, Bolaji OA, Ali H. Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation. World J Transplant 2024; 14:91146. [PMID: 38947962 PMCID: PMC11212591 DOI: 10.5500/wjt.v14.i2.91146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 04/13/2024] [Accepted: 04/25/2024] [Indexed: 06/13/2024] Open
Abstract
In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.
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Affiliation(s)
- Arthur Dilibe
- Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Lakshmi Subramanian
- Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Tracy-Ann Poyser
- Department of Medicine, Unity Health-White County Medical Center, Searcy, AR 72143, United States
| | - Osejie Oriaifo
- Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Ryan Brady
- Department of Physical Medicine and Rehab, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Sashwath Srikanth
- Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Olanrewaju Adabale
- Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Olayiwola Akeem Bolaji
- Department of Medicine, University of Maryland Capital Region Health, Largo, MD 20774, United States
| | - Hassam Ali
- Division of Gastroenterology and Hepatology, East Carolina University/Brody School of Medicine, Greenville, NC 27858, United States
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Jacobwitz M, Burstein D, Sotardi S, Maeda K, Beslow LA. A Rare Case of Late Onset Tacrolimus-Induced Leukoencephalopathy and Coma after Pediatric Orthotopic Heart Transplantation. J Heart Lung Transplant 2022; 41:1653-1655. [DOI: 10.1016/j.healun.2022.07.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/20/2022] [Accepted: 07/31/2022] [Indexed: 10/31/2022] Open
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Ismail II, Abdelnabi EA, Khan R, Al-Hashel JY, Sharfuddin KM. Tacrolimus-Induced Leukoencephalopathy in a Renal Transplantation Patient. DUBAI MEDICAL JOURNAL 2022. [DOI: 10.1159/000521790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Tacrolimus is an immunosuppressant that is frequently used following renal transplantation. Several mild neurological side effects of tacrolimus have been reported in the literature; however, severe complications in the form of confusion, seizures, and coma are rare. Herein, we report a 16-year-old boy on tacrolimus following living-donor kidney transplant, who presented with subacute onset of hand tremors, headache, altered mental status, and progressed to akinetic mute state. He was diagnosed with tacrolimus-induced leukoencephalopathy based on findings of his magnetic resonance imaging and ruling out other possible causes. He showed clinical and radiological improvement after discontinuation of tacrolimus. Radiological features of tacrolimus-induced leukoencephalopathy are more heterogenous than commonly perceived and should be suspected in such patients. The potential neurotoxicity of tacrolimus should be recognized in patients with renal transplantation, and switching to a different immunosuppressant is warranted to prevent permanent neurological damage.
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Kim WS, Paik NJ. Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. BRAIN & NEUROREHABILITATION 2021; 14:e6. [PMID: 36742107 PMCID: PMC9879417 DOI: 10.12786/bn.2021.14.e6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 03/09/2021] [Indexed: 11/08/2022] Open
Abstract
Studies using repetitive transcranial magnetic stimulation (rTMS) in healthy individuals and those with neuropsychiatric diseases have rapidly increased since the 1990s, due to the potential of rTMS to modulate the cortical excitability in the brain depending on the stimulation parameters; therefore, the safety considerations for rTMS use are expected to become more important. Wassermann published the first safety guidelines for rTMS from the consensus conference held in 1996, and Rossi and colleague then published the second safety guidelines from the multidisciplinary consensus meeting held in Siena, Italy in 2008, on behalf of the International Federation of Clinical Neurophysiology. More than 10 years after the second guidelines, the updated third safety guidelines were recently published in 2021. The general safety guidelines for conventional rTMS have not substantially changed. Because the most frequently used rTMS protocol is conventional (low- and high-frequency) rTMS in research and clinical settings, we focus on reviewing safety issues when applying conventional rTMS with a focal cortical stimulation coil. The following issues will be covered: 1) possible adverse events induced by rTMS; 2) checklists to screen for any precautions and risks before rTMS; 3) safety considerations for dosing conventional rTMS; and 4) safety considerations for using rTMS in stroke and traumatic brain injury.
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Affiliation(s)
- Won-Seok Kim
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nam-Jong Paik
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Khilari M, Panigrahi N. Tacrolimus induced diffuse pontine hyperintensity in status epilepticus: a rare entity. ADVANCES IN CLINICAL NEUROSCIENCE & REHABILITATION 2020. [DOI: 10.47795/nblh2485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Posterior Reversible Encephalopathy Syndrome resulting from the hypertension-induced Failure of cerebral autoregulation, is a well-described neuro-imaging finding resulting from vasogenic oedema. Pontine Hyperintensities resulting from this condition need recognition to prognosticate and avoid unnecessary investigations. We report a 48 year old male with chronic diabetes mellitus, Hypertension, and chronic kidney disease, and history of liver transplantation who presented with established status epilepticus. He was on Tacrolimus for prophylaxis for graft rejection. His MRI brain showed diffuse pontine and predominantly left thalamic hyperintensity, which suggested the diagnosis of central PRES. His evaluation for CNS infections and autoimmune encephalitis was negative. On stopping Tacrolimus, the imputed drug, and control of hypertension, along with dialysis, and symptomatic management for seizures, a complete recovery was observed over one week. Repeat MRI also showed partial regression of the pontine hyperintensity. This report documents the importance of this less described neuroradiological finding that can change the management significantly and have a bearing on the prognosis.
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Abstract
BACKGROUND Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. METHODS Case series and review of the literature. RESULTS We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. CONCLUSIONS Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.
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Koksel Y, Ozutemiz C, Rykken J, Ott F, Cayci Z, Oswood M, McKinney AM. "CHOICES": An acronym to aid in delineating potential causes of non-metabolic, non-infectious acute toxic leukoencephalopathy. Eur J Radiol Open 2019; 6:243-257. [PMID: 31309133 PMCID: PMC6607360 DOI: 10.1016/j.ejro.2019.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 06/16/2019] [Accepted: 06/24/2019] [Indexed: 12/18/2022] Open
Abstract
Recognition the etiologies of ATL is important due to its potentially reversible nature after treatment or removal of the toxin. “CHOICES” is useful to memorize etiologies associated with PVWM injury in non-metabolic and non-infectious ATL patients. Reduced diffusion is an early and important imaging finding to evaluate patients with non-metabolic and non-infectious ATL patients. Purpose To describe non-metabolic, non-infectious etiologies of acute toxic leukoencephalopathy (ATL) on DWI MRI, and provide a useful acronym to remember them. Material and Methods Our PACS archive was reviewed, yielding 185 patients with suspected ATL per MRI reports and clinical follow up; infectious or metabolic causes were excluded. Result/Discussion The 87 included non-infectious, non-metabolic ATL patients' etiologies are represented by the acronym 'CHOICES': chemotherapy ('C',n = 34); heroin-induced ('H',n = 6), opioid analogues ('O',n = 14); immunosuppressant ('I',n = 11) or imidazole (n = 2); cocaine ('C',n = 1); environmental or ethanol abuse ('E',n = 5), splenial lesions ('S',n = 9), and 'other' (n = 5). Conclusion The "CHOICES" acronym delineates various toxic etiologies of ATL.
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Key Words
- ADEM, Acute disseminated encephalomyelitis
- AEDs, Anti-epileptic drugs
- AHE, Acute Hepatic/Hyperammonemic Encephalopathy
- AHL, Acute hemorrhagic leukoencephalitis
- ATL, Acute toxic leukoencephalopathy
- Acute toxic leukoencephalopathy
- CO, Carbon monoxide
- Diffusion-Weighted imaging
- EPM, Extrapontine myelinolysis
- EtOH, Ethanol
- HIE, Hypoxic-ischemic encephalopathy
- LE, leukoencephalopathy
- MBD, Marchiafava-Bignami Disease
- MERS, Mild encephalitis/encephalopathy with reversible splenial lesion
- NAWM, Normal-appearing white matter
- ODS, Osmotic demyelination syndrome
- PML, Progressive multifocal leukoencephalopathy
- PRES, Posterior reversible encephalopathy syndrome
- PVWM, Periventricular white matter
- Periventricular white matter
- RIS, Radiology information system
- RSL, Reversible splenial lesions
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Affiliation(s)
- Yasemin Koksel
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Can Ozutemiz
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Jeffrey Rykken
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Frederick Ott
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Zuzan Cayci
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Mark Oswood
- Department of Radiology, Division of Neuroradiology Hennepin Healthcare Medical Center, Minneapolis, MN, USA
| | - Alexander M McKinney
- Department of Radiology, Division of Neuroradiology, University of Minnesota Medical Center, Minneapolis, MN, USA
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Seizures in patients with a phaeochromocytoma/paraganglioma (PPGL): A review of clinical cases and postulated pathological mechanisms. Rev Neurol (Paris) 2019; 175:495-505. [PMID: 31133278 DOI: 10.1016/j.neurol.2018.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Revised: 06/30/2018] [Accepted: 11/05/2018] [Indexed: 11/24/2022]
Abstract
The purpose of this work was to expound on the postulated pathological mechanisms through which pheochromocytoma/paraganglioma (PPGL) can cause seizures by conducting a comprehensive review of ten cases and several pathogenic mechanisms. The goal was to enhance awareness amongst doctors and researchers about patients with PPGL presenting with seizures. This would help decrease the risk of misdiagnosis and mismanagement in future clinics. Additionally, this review was written with the purpose to attract more attention to etiological explorations, particularly concerning rare causes of seizures, which is consistent with the idea that League Against Epilepsy (ILAE) has emphasized in the new version of the ILAE position paper published in 2017. It is of great importance to keep in mind the fact that seizures can constitute an atypical presentation of PPGL and to establish early diagnosis and accurate cure for these patients, especially in the presence of paroxysmal hypertension or other suggestive symptoms of PPGL.
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Onder H, Comba C. A very rare case of mirror syndrome presenting with concurrent posterior reversible encephalopathy syndrome. JOURNAL OF MEDICAL SCIENCES 2019. [DOI: 10.4103/jmedsci.jmedsci_25_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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10
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Weider M, Starost LJ, Groll K, Küspert M, Sock E, Wedel M, Fröb F, Schmitt C, Baroti T, Hartwig AC, Hillgärtner S, Piefke S, Fadler T, Ehrlich M, Ehlert C, Stehling M, Albrecht S, Jabali A, Schöler HR, Winkler J, Kuhlmann T, Wegner M. Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning. Nat Commun 2018; 9:899. [PMID: 29500351 PMCID: PMC5834605 DOI: 10.1038/s41467-018-03336-3] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 02/05/2018] [Indexed: 02/06/2023] Open
Abstract
Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation of the myelination program requires several transcription factors including Sox10, Olig2, and Nkx2.2. Functional interactions among them are poorly understood and important components of the regulatory network are still unknown. Here, we identify Nfat proteins as Sox10 targets and regulators of oligodendroglial differentiation in rodents and humans. Overall levels and nuclear fraction increase during differentiation. Inhibition of Nfat activity impedes oligodendrocyte differentiation in vitro and in vivo. On a molecular level, Nfat proteins cooperate with Sox10 to relieve reciprocal repression of Olig2 and Nkx2.2 as precondition for oligodendroglial differentiation and myelination. As Nfat activity depends on calcium-dependent activation of calcineurin signaling, regulatory network and oligodendroglial differentiation become sensitive to calcium signals. NFAT proteins are also detected in human oligodendrocytes, downregulated in active multiple sclerosis lesions and thus likely relevant in demyelinating disease.
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Affiliation(s)
- Matthias Weider
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Laura Julia Starost
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany.,Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany
| | - Katharina Groll
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany
| | - Melanie Küspert
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Elisabeth Sock
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Miriam Wedel
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Franziska Fröb
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Christian Schmitt
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Tina Baroti
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Anna C Hartwig
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Simone Hillgärtner
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Sandra Piefke
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Tanja Fadler
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Marc Ehrlich
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany.,Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany
| | - Corinna Ehlert
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany
| | - Martin Stehling
- Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany
| | - Stefanie Albrecht
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany
| | - Ammar Jabali
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany
| | - Hans R Schöler
- Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany
| | - Jürgen Winkler
- Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany
| | - Tanja Kuhlmann
- Institute of Neuropathology, University Hospital Münster, D-48149, Münster, Germany.
| | - Michael Wegner
- Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany.
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Villelli NW, Prevedello DM, Ikeda DS, Montaser AS, Otto BA, Carrau RL. Posterior Reversible Encephalopathy Syndrome Causing Vision Loss After Endoscopic Endonasal Resection of Pituitary Adenoma. World Neurosurg 2017; 100:708.e1-708.e10. [PMID: 28214641 DOI: 10.1016/j.wneu.2017.02.050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 02/07/2017] [Accepted: 02/08/2017] [Indexed: 11/26/2022]
Abstract
BACKGROUND Posterior reversible encephalopathy syndrome (PRES) is characterized by headache, altered mental status, visual changes, and seizure combined with brain imaging consistent with cerebral edema without infarction. To the best of our knowledge, we report the first case of PRES after an endoscopic endonasal resection of a pituitary macroadenoma. CASE DESCRIPTION A 59-year-old woman was diagnosed with a pituitary macroadenoma, for which she underwent endoscopic endonasal extracapsular resection. After an uneventful initial postoperative recovery, the patient experienced sudden onset of emesis, confusion, vision loss, and severe hypertension. Emergent computed tomography showed normal postoperative changes, with no signs of hematoma or infarction. Magnetic resonance imaging (MRI) showed fluid-attenuated inversion recovery changes in the posterior lobes and thalamus, consistent with PRES. Cerebral angiography showed no vascular abnormalities. Blood pressure control was the primary treatment modality. Within 10 days, the patient was neurologically intact except for right homonymous hemianopsia. Follow-up MRI showed resolution of the PRES with an area of infarction in the left occipital lobe. At 5 years follow-up, the patient reported minimal blurred vision. MRI showed encephalomalacia at the old infarct area, and her visual field testing was unremarkable. CONCLUSIONS Although rare in neurosurgical patients, PRES must be considered in patients who develop acute vision loss and mental status changes associated with hypertension after surgery, including endoscopic endonasal surgery. PRES has the potential for significant neurologic morbidity, if not treated in a timely manner. Early recognition and treatment, with blood pressure control mainly, are therefore mandatory after a surgical complication, such as a postoperative hematoma, has been ruled out.
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Affiliation(s)
- Nicolas W Villelli
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Daniel M Prevedello
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
| | - Daniel S Ikeda
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Alaa S Montaser
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Department of Neurological Surgery, Ain Shams University, Cairo, Egypt
| | - Bradley A Otto
- Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Ricardo L Carrau
- Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Hinduja A, Habetz K, Raina SK, Fitzgerald RT. Predictors of intensive care unit utilization in patients with posterior reversible encephalopathy syndrome. Acta Neurol Belg 2017; 117:201-206. [PMID: 27680733 DOI: 10.1007/s13760-016-0703-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Accepted: 09/21/2016] [Indexed: 10/20/2022]
Abstract
Posterior reversible encephalopathy syndrome (PRES) is an acute neurological syndrome that requires prompt, aggressive management to improve outcomes. Our aim was to identify factors that would necessitate care in the intensive care unit (ICU) in patients with PRES and the outcomes on discharge following ICU stay. We retrospectively reviewed the medical records and radiological data of adult PRES patients admitted to our tertiary care medical center. We dichotomized them into two groups based on their need for ICU care and compared their clinical, laboratory, imaging characteristics and discharge outcomes. Outcomes were defined using the modified Rankin Score (mRS) and Glasgow Outcome Score (GOS) on discharge. Out of 100 patients, 67 % required admission to the ICU. On univariate analysis, factors associated with ICU admission were atrial fibrillation (19.4 vs 0 %; p ≤ 0.05), encephalopathy from PRES (89.6 vs 66.7 %; p < 0.05), low Glasgow Coma Score (GCS) (11 ± 4 vs 14 ± 2; p = 0.01) and cortical involvement on imaging (89.6 vs 72.7 %, p = 0.03). On multivariate logistic regression analysis, encephalopathy (odds ratio 10.22; 95 % CI (1.14-91.55; p = 0.04) was the sole predictor of ICU utilization. This correlated with a GCS <12 (odds ratio 5.53; 95 % CI (1.05-29.22; p = 0.04). Despite worse functional outcomes following ICU care based on mRS (2.3 ± 2.1 vs 1.3 ± 1.4, p = 0.02) and GOS (3.9 ± 1.3 vs 4.6 ± 0.7, p ≤ 0.05), only a borderline increase in mortality was observed (10.4 vs 0 %, p = 0.05). The presence of PRES-related encephalopathy might aid in prompt identification of patients who require ICU care.
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Hashimoto K, Costa G, Khanna A, Fujiki M, Quintini C, Abu-Elmagd K. Recent Advances in Intestinal and Multivisceral Transplantation. Adv Surg 2016; 49:31-63. [PMID: 26299489 DOI: 10.1016/j.yasu.2015.04.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Koji Hashimoto
- Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Guilherme Costa
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA
| | - Ajai Khanna
- Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Masato Fujiki
- Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Cristiano Quintini
- Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Kareem Abu-Elmagd
- Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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Shijo T, Nishiyama S, Mukai Y, Tateyama M, Kuroda H, Aoki M. A mismatch between MRI lesions and SPECT hypoperfusion in tacrolimus-related encephalopathy. J Neurol Sci 2016; 367:308-10. [PMID: 27423609 DOI: 10.1016/j.jns.2016.06.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 05/27/2016] [Accepted: 06/16/2016] [Indexed: 10/21/2022]
Affiliation(s)
- Tomomi Shijo
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
| | - Shuhei Nishiyama
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
| | - Yoshiyuki Mukai
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
| | - Maki Tateyama
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
| | - Hiroshi Kuroda
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
| | - Masashi Aoki
- Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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Rodríguez-González MJ, Calvo-Betancourt LS, Echeverría-Correa LE. Síndrome de encefalopatía posterior reversible secundaria a tacrolimus. REVISTA COLOMBIANA DE CARDIOLOGÍA 2016. [DOI: 10.1016/j.rccar.2015.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Singer S, Grommes C, Reiner AS, Rosenblum MK, DeAngelis LM. Posterior Reversible Encephalopathy Syndrome in Patients With Cancer. Oncologist 2015; 20:806-11. [PMID: 26032137 DOI: 10.1634/theoncologist.2014-0149] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Accepted: 03/05/2015] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Posterior reversible encephalopathy syndrome (PRES) is characterized by neurologic symptoms with typical lesions on neuroimaging and may be associated with chemotherapy and immunosuppressive agents used in patients with cancer. We described the spectrum of PRES at a major cancer center. METHODS We reviewed charts of adults with PRES between 2005 and 2011 at Memorial Sloan Kettering Cancer Center for clinical information and outcome. RESULTS We identified 21 women (68%) and 10 men (median cohort age: 58 years). Solid tumors (n = 22, 71%) were more common than hematologic (n = 8) or primary brain malignancies (n = 1). Prior brain irradiation (16%) and central nervous system metastases (10%) were uncommon. There were 55% who received chemotherapy or targeted therapy within the month preceding PRES, including 6 patients who received bevacizumab; PRES followed allogeneic stem cell transplantation in 5 (16%). Presenting symptoms included confusion (71%), seizure (58%), and headache (48%). Maximum systolic and diastolic blood pressures were similar among patients grouped by cancer type, chemotherapy or bevacizumab use, and atypical imaging. Moreover, 37% of patients with both magnetic resonance imaging (MRI) and computed tomography (CT) had normal CT concurrent with PRES on MRI, and 84% returned to neurologic baseline at a median of 7.5 days (range: 1-167 days) from onset. Successful anticonvulsant taper was achieved in 51%. Chemotherapy rechallenge was attempted in 41% without recurrent PRES. Autopsy revealed nonspecific changes isolated to radiographically affected areas in one of two patients. CONCLUSION Recent chemotherapy, particularly bevacizumab, is common in cancer patients with PRES. Clinical and radiographic presentations may vary; MRI appears more sensitive than CT. Anticonvulsant taper and chemotherapy rechallenge is often possible. IMPLICATIONS FOR PRACTICE Posterior reversible encephalopathy syndrome is characterized by neurologic symptoms with typical lesions on neuroimaging and may be associated with chemotherapy and immunosuppressive agents used in patients with cancer. Clinical and radiographic presentations are protean, and magnetic resonance imaging is more sensitive than computed tomography. Recovery is common, and many patients can be successfully rechallenged with the apparently offending chemotherapy agent or regimen.
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Affiliation(s)
- Samuel Singer
- Departments of Neurology, Epidemiology and Biostatistics, and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Christian Grommes
- Departments of Neurology, Epidemiology and Biostatistics, and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Anne S Reiner
- Departments of Neurology, Epidemiology and Biostatistics, and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Marc K Rosenblum
- Departments of Neurology, Epidemiology and Biostatistics, and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Lisa M DeAngelis
- Departments of Neurology, Epidemiology and Biostatistics, and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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Valone F, Lieberman JA, Burch S. Postoperative Blindness Due to Posterior Reversible Encephalopathy Syndrome Following Spine Surgery: A Case Report and Review of the Literature. JBJS Case Connect 2014; 4:e30. [PMID: 29252570 DOI: 10.2106/jbjs.cc.m.00222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Affiliation(s)
- Frank Valone
- Departments of Orthopaedic Surgery (F.V. and S.B.) and Anesthesia and Perioperative Care (J.A.L.), University of California, San Francisco, 500 Parnassus Avenue, MU 320W, San Francisco, CA 94143.
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Azuma T, Oishi M, Takei M, Sawada S. Tacrolimus-related nocturnal myoclonus of the lower limbs in elderly patients with rheumatoid arthritis. Mod Rheumatol 2014. [DOI: 10.3109/s10165-007-0574-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Wijdicks EF, Hocker SE. Neurologic complications of liver transplantation. HANDBOOK OF CLINICAL NEUROLOGY 2014; 121:1257-66. [DOI: 10.1016/b978-0-7020-4088-7.00085-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2023]
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Abstract
Complex multiorgan failure may require simultaneous transplantation of several organs, including heart-lung, kidney-pancreas, or multivisceral transplantation. Solid organ transplantation can also be combined with hematopoietic stem cell transplantation to modulate immunologic response to a solid organ allograft. Combined multiorgan transplantation may offer a lower rate of allograft rejection and lower immunosuppression needs. In recent years, intestinal and multivisceral transplantations became viable as a rescue treatment for patients with irreversible intestinal failure who can no longer tolerate total parenteral nutrition with 70% survival after 5 years which is comparable to other types of solid organ allografts. Post-transplant neurologic complications were reported in up to 86% of allograft recipients and greatly overlap in intestinal and multivisceral allograft recipients, without a significant effect on the outcome of transplantation. Other common organ combinations in multiorgan transplantation include kidney-pancreas, which is mostly used for patients with renal failure and uncontrolled diabetes, and heart-lung for patients with congenital heart disease and idiopathic pulmonary arterial hypertension. Kidney-pancreas transplantation frequently results in an improvement of diabetic complications, including diabetic neuropathy. Heart-lung allograft recipients have very similar clinical course and spectrum of neurologic complications to lung transplant recipients. At this time there are no reports of an increased risk of graft-versus-host disease with combined transplantation of solid organ allograft and hematopoietic stem cells. Chronic immunosuppression and complex toxic-metabolic disturbances after multiorgan transplantation create a permissive environment for development of a wide spectrum of neurologic complications which largely resemble complications after transplantations of individual components of complex multiorgan allografts.
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Affiliation(s)
- Saša A Zivković
- Neurology Service, Department of Veterans Affairs and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Živković SA. Neurologic complications after liver transplantation. World J Hepatol 2013; 5:409-416. [PMID: 24023979 PMCID: PMC3767839 DOI: 10.4254/wjh.v5.i8.409] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 06/21/2013] [Accepted: 07/13/2013] [Indexed: 02/06/2023] Open
Abstract
Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.
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Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation. Ann Surg 2012; 256:494-508. [PMID: 22868368 DOI: 10.1097/sla.0b013e318265f310] [Citation(s) in RCA: 132] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation. BACKGROUND Despite continual improvement in early survival, the long-term therapeutic efficacy of visceral transplantation has yet to be defined. METHODS A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone. Clinical data were used to assess outcome including graft function and long-term survival predictors. The socioeconomic milestones and QOL measures were assessed by clinical evaluation, professional consultation, and validated QOL inventory. RESULTS Of 376 recipients, 227 survived beyond 5 years, with conditional survival of 75% at 10 years and 61% at 15 years. With a mean follow-up of 10 ± 4 years, 177 (92 adults, 85 children) are alive, with 118 (67%) recipients 18 years or older. Nonfunctional social support and noninclusion of the liver in the visceral allograft are the most significant survival risk factors. Nutritional autonomy was achievable in 160 (90%) survivors, with current serum albumin level of 3.7 ± 0.5 gm/dL and body mass index of 25 ± 6 kg/m(2). Despite coexistence or development of neuropsychiatric disorders, most survivors were reintegrated to society with self-sustained socioeconomic status. In parallel, most of the psychological, emotional, and social QOL measures significantly (P < 0.05) improved after transplantation. Current morbidities with potential impact on global health included dysmotility (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with significantly (P < 0.05) higher incidence among adult recipients. CONCLUSIONS With new tactics to further improve long-term survival including social support measures, visceral transplantation has achieved excellent nutritional autonomy and good QOL.
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Herynek V, Wagnerová D, Hejlová I, Dezortová M, Hájek M. Changes in the brain during long-term follow-up after liver transplantation. J Magn Reson Imaging 2012; 35:1332-7. [DOI: 10.1002/jmri.23599] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 12/29/2011] [Indexed: 12/18/2022] Open
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Pustavoitau A, Bhardwaj A, Stevens R. Analytic Review: Neurological Complications of Transplantation. J Intensive Care Med 2011; 26:209-22. [DOI: 10.1177/0885066610389549] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders—often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents.
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Affiliation(s)
- Aliaksei Pustavoitau
- Departments of Anesthesiology Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anish Bhardwaj
- Departments of Neurology and Neurological Surgery, Tufts University School of Medicine, Boston, MA, USA,
| | - Robert Stevens
- Departments of Anesthesiology Critical Care Medicine, Neurology, Neurosurgery, and Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Spada M, Corno V, Colledan M, Segalin A, Lucianetti A, Torre G, Riva S, Sonzogni A, Petz W, Gridelli B. Rejection and tacrolimus conversion therapy in paediatric liver transplantation. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb02056.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
Posterior reversible encephalopathy syndrome (PRES) is characterized by headache, altered mental status, visual disturbances, and seizures. Radiological features typically include edema of the posterior cerebral regions, especially of the parietooccipital lobes. Atypical imaging features, such as involvement of anterior cerebral regions, deep white matter, and the brain stem are also frequently seen. Vasoconstriction is common in vascular imaging. Different conditions have been associated with PRES, but toxemia of pregnancy, solid organ or bone marrow transplantation, immunosuppressive treatment, cancer chemotherapy, autoimmune diseases, and hypertension are most commonly described. The pathophysiology of PRES is unclear and different hypotheses are being discussed. Posterior reversible encephalopathy syndrome is best managed by monitoring and treatment in the setting of a neurointensive care unit. The prognosis is usually benign with complete reversal of clinical symptoms within several days, when adequate treatment is immediately initiated. Treatment of severe hypertension, seizures, and withdrawal of causative agents represent the hallmarks of specific therapy in PRES. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Therefore, awareness of PRES is of crucial importance for the intensivist.
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Affiliation(s)
- Dimitre Staykov
- Neurology Department, University of Erlangen-Nuremberg, Germany.
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Burnett MM, Hess CP, Roberts JP, Bass NM, Douglas VC, Josephson SA. Presentation of reversible posterior leukoencephalopathy syndrome in patients on calcineurin inhibitors. Clin Neurol Neurosurg 2010; 112:886-91. [DOI: 10.1016/j.clineuro.2010.07.023] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Revised: 07/19/2010] [Accepted: 07/31/2010] [Indexed: 11/28/2022]
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Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010; 85:427-32. [PMID: 20435835 PMCID: PMC2861971 DOI: 10.4065/mcp.2009.0590] [Citation(s) in RCA: 582] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To identify and define clinical associations and radiologic findings of posterior reversible encephalopathy syndrome (PRES). PATIENTS AND METHODS Patients prospectively diagnosed as having PRES from October 1, 2005, through April 30, 2009, were pooled with retrospectively identified patients admitted from August 1, 1999, through September 30, 2005. We performed a detailed review of clinical information, including demographics, presenting symptoms, medical history, and risk factors. All patients underwent computed tomography of the brain or magnetic resonance imaging. Findings on magnetic resonance imaging were analyzed independently by 2 neuroradiologists. RESULTS We identified 120 cases of PRES in 113 patients (mean age, 48 years). Mean peak systolic blood pressure was 199 mm Hg (minimum-maximum, 160-268 mm Hg), and mean peak diastolic blood pressure was 109 mm Hg (minimum-maximum, 60-144 mm Hg). Etiologies of PRES included hypertension (n=69 [61%]), cytotoxic medications (n=21 [19%]), sepsis (n=8 [7%]), preeclampsia or eclampsia (n=7 [6%]), and multiple organ dysfunction (n=1 [1%]). Autoimmune disease was present in 51 patients (45%). Clinical presentations included seizures (n=84 [74%]), encephalopathy (n=32 [28%]), headache (n=29 [26%]), and visual disturbances (n=23 [20%]). In the 115 cases (109 patients) for which magnetic resonance imaging findings were available, the parieto-occipital regions were the most commonly involved (n=108 [94%]), followed by the frontal lobe (n=88 [77%]), temporal lobe (n=74 [64%]), and cerebellum (n=61 [53%]). Cerebellar involvement was significantly more frequent in patients with a history of autoimmunity (P=.008), and patients with sepsis were more likely to have cortical involvement (P<.001). CONCLUSION A substantial proportion of patients with PRES have underlying autoimmune conditions that may support endothelial dysfunction as a pathophysiologic mechanism. On brain imaging, the location and severity of vasogenic edema were mostly similar for the different clinical subgroups.
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Affiliation(s)
| | | | | | | | | | - Alejandro A. Rabinstein
- Individual reprints of this article are not available. Address correspondence to Alejandro A. Rabinstein, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 ()
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Sharief U, Perry DJ. Delayed reversible posterior encephalopathy syndrome following chemotherapy with oxaliplatin. Clin Colorectal Cancer 2010; 8:163-5. [PMID: 19632931 DOI: 10.3816/ccc.2009.n.026] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Reversible posterior leukoencephalopathy (RPLS), also known as posterior reversible encephalopathy syndrome, is characterized by magnetic resonance imaging (MRI) findings of reversible vasogenic subcortical edema without infarction. The clinical presentation is usually nonspecific and typically involves global encephalopathy, seizures, headache, or visual symptoms. MRI of the brain is essential to the diagnosis of RPLS. Typical findings of RPLS include high-intensity signal on T2-weighted images predominantly in the posterior lobes of the brain that is caused by subcortical white matter vasogenic edema. Fluid-attenuated inversion recovery (FLAIR) sequences on MRI improve sensitivity and detect subtle peripheral lesions. This clinical radiographic syndrome has been described in a number of medical conditions, with hypertensive encephalopathy, eclampsia, and the use of immunosuppressant drugs (most notably calcineurin inhibitors) being the most common. It has occasionally been reported with cisplatin and rarely with carboplatin. Its occurrence with oxaliplatin is very unusual. An extensive literature search including PUBMED and direct contact with the drug manufacturer yielded only 2 known case reports. Herein, we describe a case that had classic clinical and radiologic features of RPLS. We also briefly describe 2 other patients who have been described to have RPLS with oxaliplatin in the literature.
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Abstract
Neurologic complications affect posttransplant recovery of more than 20% of transplant recipients. Etiology is usually related to surgical procedure of transplantation, primary disorders causing failure of transplanted organ, opportunistic infections, and neurotoxicity of immunosuppressive medications. Risk of opportunistic infections and immunosuppressant neurotoxicity is greatest within the first six months, but it persists along with long-term maintenance immunosuppression required to prevent graft rejection. Neurotoxicity may require alteration of immunosuppressive regimen, and prompt therapy of opportunistic infections improves outcomes.
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Affiliation(s)
- Sasa A Zivković
- Neurology Service, VA Pittsburgh Healthcare System, University Drive C, Pittsburgh, PA 15240, USA.
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Courand PY, Christin F, Ben Cheikh A, Baillon JJ, Ber CE, Rimmelé T. [Posterior reversible encephalopathy related to tacrolimus in a liver transplanted HIV patient]. ACTA ACUST UNITED AC 2009; 34:29-34. [PMID: 19781881 DOI: 10.1016/j.gcb.2009.07.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2009] [Revised: 05/01/2009] [Accepted: 07/03/2009] [Indexed: 11/18/2022]
Abstract
Tacrolimus-related posterior reversible leukoencephalopathy (PRLE) is a rare complication which should be recognized by clinicians who regularly use immunosuppressive therapy. We report the case of an HIV-positive, hepatitis C-positive liver transplant patient who presented with this complication. Immunosuppression with tacrolimus was started after postsurgery. On the 20th day, the patient suffered two tonic-clonic convulsive attacks against a background of hypertension. Cerebral magnetic resonance imaging and lumbar puncture led to diagnosis of tacrolimus-related PRLE after eliminating other possible diagnoses. Therapeutic management consisted of withdrawing tacrolimus and initiating treatment with antiepileptogenic and antihypertensive drugs, supplemented with magnesium sulphate. The symptoms regressed in the days following withdrawal of tacrolimus and the majority of lesions on magnetic resonance imaging disappeared within two weeks. The aim of which should be to identify patients at risk of developing this complication. This would enable targeted prevention involving magnesium supplementation, strict control of blood pressure and serial monitoring of tacrolimus blood concentrations.
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Affiliation(s)
- P-Y Courand
- Département d'anesthésie-réanimation, pavillon P réanimation, hôpital Edouard-Herriot, place d'Arsonval, 69003 Lyon, France.
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Manfro R, Vedolin L, Cantarelli M, Oppitz P, Antunes A, Rieder C. Progressive multifocal leukoencephalopathy in a kidney transplant recipient after conversion to mycophenolic acid therapy. Transpl Infect Dis 2009; 11:189-90. [DOI: 10.1111/j.1399-3062.2009.00368.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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The spectrum of thrombotic thrombocytopenic purpura: a clinicopathologic demonstration of tacrolimus-induced thrombotic thrombocytopenic purpura in a lung transplant patient. South Med J 2009; 101:744-7. [PMID: 18580733 DOI: 10.1097/smj.0b013e3181792687] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Immunosuppressive drugs used post-transplantation are among the most common causes of thrombotic thrombocytopenic purpura (TTP). Diagnosis is often confounded not only by its myriad presentations, but also because these manifestations may be explained by the comorbidities or complications of transplantation. A 61-year-old female who had a single lung transplant for severe chronic obstructive pulmonary disease maintained on corticosteroids, tacrolimus and mycophenolate mofetil, was admitted for fever, headache with confusion and lethargy. She was mildly anemic and thrombocytopenic. Peripheral smear showed rare fragmented red cells. Muddy brown casts were present on urinalysis. She was diagnosed with TTP. Tacrolimus was discontinued and the mental status of the patient, anemia and thrombocytopenia improved significantly.
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Horbinski C, Bartynski WS, Carson-Walter E, Hamilton RL, Tan HP, Cheng S. Reversible encephalopathy after cardiac transplantation: histologic evidence of endothelial activation, T-cell specific trafficking, and vascular endothelial growth factor expression. AJNR Am J Neuroradiol 2009; 30:588-90. [PMID: 18854444 DOI: 10.3174/ajnr.a1311] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Reversible encephalopathy after transplantation is well recognized. The condition is commonly thought to be related to immune suppression, and a characteristic brain imaging pattern is typically recognized with vasogenic edema in the parietal and occipital regions, typically termed posterior reversible encephalopathy syndrome (PRES). We report the case of a patient with reversible encephalopathy after cardiac transplantation with brain biopsy evidence of endothelial activation, selective intravascular/perivascular T-cell trafficking, and VEGF expression in astrocytes, neurons, and the endothelium.
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Affiliation(s)
- C Horbinski
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Aranas RM, Prabhakaran S, Lee VH. Posterior reversible encephalopathy syndrome associated with hemorrhage. Neurocrit Care 2009; 10:306-12. [PMID: 19225908 DOI: 10.1007/s12028-009-9200-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2008] [Accepted: 01/29/2009] [Indexed: 12/29/2022]
Abstract
BACKGROUND Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological entity characterized by headache, encephalopathy, visual disturbances, and seizures in association with reversible vasogenic edema on neuroimaging. Intracerebral hemorrhage associated with PRES (PRES-ICH) is generally considered an atypical finding. METHODS Retrospective case series. RESULTS Seven patients were identified with PRES-ICH, four males and three females. The presenting clinical symptoms included headache (2), encephalopathy (5), vision changes (2), seizures (2), and hemiparesis (1). The co-morbid conditions included acute renal dysfunction (3), solid organ transplantation (3), bone marrow transplant (1), use of calcineurin inhibitor agents (4), and pre-eclampsia (1). Neuroimaging revealed intraparenchymal hemorrhage in six patients and subarachnoid hemorrhage in one patient. Six of the seven patients with PRES-related ICH had underlying bleeding diathesis, including one patient who was anti-coagulated with a heparin drip. The mean platelet count was 82.1 x 10(3)/microl (range, 4-232 x 10(3)/microl), and the mean INR value was 2.18 (range, 0.9-6.7). Two patients died during the acute hospitalization. Among the five survivors, only two patients had good functional outcome (pre-defined as mRS < or = 1). CONCLUSION In our series, the majority of patients with PRES-ICH (85%) had an underlying bleeding diathesis or coagulopathy. Although PRES is typically considered to have a favorable prognosis, the clinical outcome of PRES with associated ICH can be more variable.
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Affiliation(s)
- Rosalyn M Aranas
- Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison St #1121, Chicago, IL 60612, USA
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FK1706, a novel non-immunosuppressive immunophilin ligand, modifies the course of painful diabetic neuropathy. Neuropharmacology 2008; 55:1226-30. [DOI: 10.1016/j.neuropharm.2008.07.048] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2008] [Revised: 07/17/2008] [Accepted: 07/29/2008] [Indexed: 11/18/2022]
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Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008; 29:1036-42. [PMID: 18356474 DOI: 10.3174/ajnr.a0928] [Citation(s) in RCA: 707] [Impact Index Per Article: 41.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state coupled with a unique CT or MR imaging appearance. Recognized in the setting of a number of complex conditions (preeclampsia/eclampsia, allogeneic bone marrow transplantation, organ transplantation, autoimmune disease and high dose chemotherapy) the imaging, clinical and laboratory features of this toxic state are becoming better elucidated. This review summarizes the basic and advanced imaging features of PRES, along with pertinent features of the clinical and laboratory presentation and available histopathology. Many common imaging/clinical/laboratory observations are present among these patients, despite the perception of widely different associated clinical conditions.
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Affiliation(s)
- W S Bartynski
- Department of Radiology, Division of Neuroradiology, University of Pittsburgh, Presbyterian University Hospital, Pittsburgh, PA 15213, USA.
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Amodio P, Biancardi A, Montagnese S, Angeli P, Iannizzi P, Cillo U, D'Amico D, Gatta A. Neurological complications after orthotopic liver transplantation. Dig Liver Dis 2007; 39:740-7. [PMID: 17611177 DOI: 10.1016/j.dld.2007.05.004] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2006] [Revised: 05/08/2007] [Accepted: 05/08/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND The number of orthotopic liver transplantation performed each year is increasing due to increased safety and logistic facilities. Therefore, the importance of reducing adverse events is progressively growing. AIM To review present knowledge on the neurological complications of orthotopic liver transplantation. METHODS The epidemiology, the clinical features and the pathophysiology of the neurological complications of orthotopic liver transplants, resulting from a systematic review of the literature in the last 25 years, are summarized. RESULTS AND CONCLUSIONS The review highlights that a relevant variety of neurological adverse events can occur in patients undergoing orthotopic liver transplantation. The knowledge of neurological complications of orthotopic liver transplantation is important for transplantation teams to reduce their prevalence and improve their management. In addition, the likelihood of neurological adverse effects provides evidence for the need of a careful cognitive and neurological work up of patients in the orthotopic liver transplantation waiting list, in order to recognize and interpret neurological dysfunction occurring after orthotopic liver transplantation.
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Affiliation(s)
- P Amodio
- Clinical Medicine 5 and Veneto Regional Reference Centre for Hepatic Diseases, University of Padova, Padova, Italy.
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Azuma T, Oishi M, Takei M, Sawada S. Tacrolimus-related nocturnal myoclonus of the lower limbs in elderly patients with rheumatoid arthritis. Mod Rheumatol 2007; 17:247-50. [PMID: 17564783 DOI: 10.1007/s10165-007-0574-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2006] [Accepted: 01/15/2007] [Indexed: 10/23/2022]
Abstract
Tacrolimus is an effective and well-tolerated treatment for rheumatoid arthritis (RA). We report three cases of strictly sleep-associated myoclonus in RA patients treated with tacrolimus. Although the high-dosage administration of tacrolimus in transplantation is known to cause diverse neurotoxic adverse effects, including myoclonus, no previous cases of myoclonus in RA, especially in association with sleep, have been reported. We suggest that this is not a rare adverse effect, particularly in elderly RA patients.
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Affiliation(s)
- Takanori Azuma
- Department of Rheumatology, Saitama Hospital, Kawagoe, Japan.
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40
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Abstract
Neurologic complications are common after transplantation and affect 30-60% of transplant recipients. The etiology of most of the posttransplant neurologic disorders is related to the opportunistic infections, both systemic and involving central nervous system (CNS), toxicity of immunosuppressive medications, and the metabolic insult created by the underlying primary disease and the transplant procedure. Neuroimaging studies are one of the key tools in the evaluation and enable early diagnosis of neurologic complications in transplant patients, especially posterior reversible leukoencephalopathy syndrome, central pontine myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses. Magnetic resonance imaging (MRI) is the preferred technique, but each of the available neuroimaging techniques offers a unique insight into the pathophysiologic mechanisms underlying neurologic complications of transplantation. The role of neuroimaging in this population includes early detection of calcineurin inhibitor neurotoxicity, opportunistic infections, neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can monitor longitudinal progression of disease and treatment response.
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Affiliation(s)
- Sasa Zivković
- VA Pittsburgh HCS and Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
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41
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Liu D, McIlvain HB, Fennell M, Dunlop J, Wood A, Zaleska MM, Graziani EI, Pong K. Screening of immunophilin ligands by quantitative analysis of neurofilament expression and neurite outgrowth in cultured neurons and cells. J Neurosci Methods 2007; 163:310-20. [PMID: 17490751 DOI: 10.1016/j.jneumeth.2007.03.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2007] [Revised: 03/22/2007] [Accepted: 03/22/2007] [Indexed: 02/04/2023]
Abstract
Immunophilins are protein receptors for the immunosuppressant drugs FK506, cyclosporin A (CsA), and rapamycin. Two categories of immunophilins are the FK506-binding proteins (FKBPs), which bind to FK506, rapamycin, and CCI-779 and the cyclophilins, which bind to CsA. Reports have shown that immunophilins are expressed in the brain and spinal cord, are 10-100-fold higher in CNS tissue than immune tissue, and their expression is increased following nerve injury, suggesting that their chemical ligands may have therapeutic utility in the treatment of neurodegenerative diseases. In this study, we report the development and utility of a rapid neurofilament (NF) enzyme-linked immunosorbent assay (ELISA) to quantify neuronal survival and the Cellomics ArrayScan platform to quantify neurite outgrowth following treatment with immunophilin ligands. Cultured neurons or F-11 cells were treated with various immunophilin ligands for 72 or 96h and their promotion of neuronal survival and neurite outgrowth were determined. The results showed that all immunophilin ligands, in a concentration-dependent manner, significantly increased neuronal survival and neurite outgrowth, when compared to control cultures. Taken together, these results demonstrate the potential utility of the neurofilament ELISA and Cellomics ArrayScan platform to efficiently quantify neurotrophic effects of immunophilin ligands on cultured neurons and cell lines.
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Affiliation(s)
- Danni Liu
- Neuroscience Discovery Research, Wyeth Research, Princeton, NJ 08543, United States
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42
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Alehan F, Erol I, Agildere AM, Ozcay F, Baskin E, Cengiz N, Alioglu B, Haberal M. Posterior leukoencephalopathy syndrome in children and adolescents. J Child Neurol 2007; 22:406-13. [PMID: 17621519 DOI: 10.1177/0883073807301932] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Posterior leukoencephalopathy syndrome is a recently identified clinical and radiologic entity. The characteristic radiologic findings are bilateral gray and white matter edema in the posterior regions of the cerebral hemispheres. This article reports clinical and radiologic findings in 10 consecutive episodes of posterior leukoencephalopathy syndrome that were diagnosed in 9 children and adolescents. The causes were immunosuppressive therapy in 7 patients and a combination of renal failure and hypertension in 3. The most common presenting symptoms were seizure and altered consciousness; others included headache, sixth nerve palsy, and cortical blindness. Imaging demonstrated abnormalities in the parietal and occipital lobes in all 10 episodes. The signs and symptoms resolved after immunosuppressive agents were reduced or discontinued, or after uremia and hypertension were corrected. Four patients underwent follow-up cranial imaging, and the images showed nearly complete or complete resolution. The syndrome was clinically reversible in all patients.
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Affiliation(s)
- Füsun Alehan
- Department of Pediatrics (Divisions of Neurology), Başkent University Faculty of Medicine, Ankara, Turkey
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43
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Alemdar AY, Sadi D, McAlister V, Mendez I. Intracerebral co-transplantation of liposomal tacrolimus improves xenograft survival and reduces graft rejection in the hemiparkinsonian rat. Neuroscience 2007; 146:213-24. [PMID: 17303340 DOI: 10.1016/j.neuroscience.2007.01.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2006] [Revised: 12/26/2006] [Accepted: 01/08/2007] [Indexed: 01/19/2023]
Abstract
Immunosuppression remains a key issue in neural transplantation. Systemic administration of cyclosporin-A is currently widely used but has many severe adverse side effects. Newer immunosuppressive agents, such as tacrolimus (TAC) and rapamycin (RAPA), have been investigated for their neuroprotective properties on dopaminergic neurons. These drugs have been formulated into liposomal preparations [liposomal tacrolimus (LTAC) and liposomal rapamycin (LRAPA)] which retain these neuroprotective properties. Due to the slower release of the drugs from the liposomes, we hypothesized that co-transplantation of either LTAC or LRAPA within a xenogeneic cell suspension would increase cell survival and decrease graft rejection in the hemiparkinsonian rat, and that a combination of the two drugs may have a synergistic effect. 6-hydroxydopamine-lesioned rats were divided to four groups which received intra-striatal transplants of the following: 1) a cell suspension containing 400,000 fetal mouse ventral mesencephalic cells; 2) the cell suspension containing 0.63 microM LRAPA; 3) the cell suspension containing a dose of 2.0 microM LTAC; 4) the cell suspension containing 2.0 microM LTAC and 0.63 microM LRAPA. Functional recovery was assessed by amphetamine-induced rotational behavior. Animals were killed at 4 days or 6 weeks post-transplantation, and immunohistochemistry was performed to look at the expression of tyrosine hydroxylase and major histocompatibility complex classes I and II. Only the group receiving LTAC had a decrease in rotational behavior. This observation correlated well with significantly more surviving tyrosine hydroxylase immunoreactive cells compared with the other groups and significantly lower levels of immunorejection as assessed by major histocompatibility complex class I and II staining. This study has shown the feasibility of using local immunosuppression in xenotransplantation. These findings may be useful in optimizing immunosuppression in experimental neural transplantation in the laboratory and its translation into the clinical setting.
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Affiliation(s)
- A Y Alemdar
- Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax Infirmary, Nova Scotia, Canada B3H 3A7
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Zipper SG, Tischendorf M, Westphal K. Postoperativ aufgetretene reversible posteriore Enzephalopathie bei einem Patientin mit Morbus Crohn. Anaesthesist 2006; 55:1064-7. [PMID: 16924516 DOI: 10.1007/s00101-006-1083-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Posterior encephalopathy (PE) is a rare condition with different origins and unknown pathogenesis. We report on a case of a 16-year-old boy with Crohn's disease who developed PE after peridural anesthesia with ropivacain. A possible connection between PE, ropivacain and Crohn's disease is discussed on the basis of the current literature.
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Affiliation(s)
- S G Zipper
- Sektion Neurologie mit klinischer Neurophysiologie, St. Marienkrankenhaus, Richard-Wagner-Str. 14, 60318 Frankfurt/Main, Deutschland.
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Nagashima T, Muroi K, Kawano-Yamamoto C, Miyoshi T, Tatara R, Meguro A, Fujiwara SI, Obara Y, Oh I, Kikuchi S, Sato K, Matsuyama T, Toshima M, Ohmine K, Ozaki K, Takatoku M, Mori M, Nagai T, Ozawa K. Pleocytosis after hemopoietic stem cell transplantation. Leuk Lymphoma 2006; 47:1613-7. [PMID: 16966274 DOI: 10.1080/10428190600625836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD) prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC transplants but in none of 11 patients receiving autologous HSC transplants. Of the 12 patients with CSF pleocytosis, only one patient developed leukoencephalopathy later. There was a correlation between CSF cell numbers and trough levels of CSA but not with those of FK506. In patients receiving allogeneic HSC transplants, CSF pleocytosis may be relatively common and may reflect neurologic damage associated with calcineurin inhibitors.
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Affiliation(s)
- Takahiro Nagashima
- Division of Cell Therapy, Jichi Medical School Hospital, Minamikawachi-machi, Kawachi-gun, Tochigi-ken, Japan
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Chegounchi M, Hanna MG, Neild GH. Progressive neurological disease induced by tacrolimus in a renal transplant recipient: case presentation. BMC Nephrol 2006; 7:7. [PMID: 16573841 PMCID: PMC1440850 DOI: 10.1186/1471-2369-7-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2005] [Accepted: 03/31/2006] [Indexed: 11/24/2022] Open
Abstract
Background Tacrolimus and cyclosporine, both calcineurin inhibitors, can cause neurological side effects. While mild symptoms such as tremor are well recognised, severe complications including seizures and encephalopathy are poorly documented following renal transplantation. Case presentation We report a 42 year old man who received a cadaver renal transplant. He received tacrolimus and prednisolone. The course was uneventful for 6 weeks when he became intermittently confused, with unsteady gait and slurred speech. Following a grand mal convulsion he was admitted. He had no focal neurological signs, cerebrospinal fluid was normal; electroencephalogram was consistent with temporal lobe partial epilepsy. The magnetic resonance imaging of brain showed widespread changes with multiple areas of low signal intensity in brain stem and cerebral hemispheres. He was readmitted 3 weeks later after further fits, despite anti-convulsant therapy. He was psychotic with visual hallucinations, and rapidly became obtunded. Although his tacrolimus blood concentration had been kept in the normal range, his symptoms improved dramatically when the tacrolimus was stopped. Conclusion Severe central nervous system toxicity from calcineurin inhibitors has been rarely reported in renal transplantation and we found only one report of tacrolimus-induced toxicity in an adult. We believe the condition is frequently undiagnosed. It is a very important diagnosis not to miss as the remedy is simple and failure may result in unnecessary brain biopsy, as well as irreversible injury.
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Affiliation(s)
- Marjan Chegounchi
- Department of Nephrology, UCL Hospitals Trust, Middlesex Hospital, W1T 3AA, London
| | - Michael G Hanna
- Department of Neurology, UCL Hospitals Trust, Middlesex Hospital, W1T 3AA, London
| | - Guy H Neild
- Department of Nephrology, UCL Hospitals Trust, Middlesex Hospital, W1T 3AA, London
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47
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Rotamase inhibitors for neurological diseases. Expert Opin Ther Pat 2005. [DOI: 10.1517/13543776.10.10.1613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Salgado OJ, Rosales BC, García R. Reversible Leukoencephalopathy Syndrome Associated to Leukopenia in a Chronic Hemodialysis Patient. Ther Apher Dial 2005; 9:69-73. [PMID: 15828910 DOI: 10.1111/j.1774-9987.2005.00207.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Reversible leukoencephalopathy syndrome (RLS) is a rare brain disorder, characterized by diffuse attenuation of cerebral white matter, which has been most commonly observed in transplant patients receiving calcineurin inhibitors or in patients with severe hypertension. We report an episode of RLS in a 22-year-old male patient on chronic hemodialysis with well-controlled moderate hypertension who presented with de novo headache and generalized seizures. Cranial magnetic resonance image (MRI) revealed multiple areas of increased signal intensity in the white matter on T2-weighed images which resolved spontaneously at subsequent MRIs. White blood cell count showed leucopenia with normal CD4 count at flow cytometry. A viral etiology could not be demonstrated. Reversible leukoencephaolopathy syndrome symptoms remitted within 72 h but leukopenia persisted over 10 months. The patient received a kidney transplant 15 months after RLS onset and has received cyclosporine since the second post-transplant day. No recurrence of RLS symptoms has been observed. The etiology of the MRI changes in the present case seemed not to be either vasogenic or cytotoxic.
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Affiliation(s)
- Octavio J Salgado
- Center of Experimental Surgery and Medicine, University of Zulia, Apartado Postal 313, Marracaibo, Venezuela.
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49
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Lavigne CM, Shrier DA, Ketkar M, Powers JM. Tacrolimus leukoencephalopathy: A neuropathologic confirmation. Neurology 2004; 63:1132-3. [PMID: 15452321 DOI: 10.1212/01.wnl.0000138568.60774.e4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Catherine M Lavigne
- University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
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50
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Kaczmarek I, Groetzner J, Meiser B, Mueller M, Landwehr P, Ueberfuhr P, Bruning R, Reichart B. Impairment of the blood-brain barrier can result in tacrolimus-induced reversible leucoencephalopathy following heart transplantation. Clin Transplant 2004; 17:469-72. [PMID: 14703933 DOI: 10.1034/j.1399-0012.2003.00071.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Fatal leucoencephalopathy is a rare calcineurin inhibitor-related complication, especially in kidney and liver transplant recipients. The only means of clinical management reported so far is the discontinuation or reduction in the calcineurin inhibitor. We herein report a case of a 37-yr-old male who developed leucoencephalopathy 12 wk after heart transplantation and recovered after stabilization of metabolism and arterial blood pressure. The findings in this case support the hypothesis that tacrolimus-associated neurotoxicity is severely increased by an impairment of the blood-brain barrier. Withdrawal of tacrolimus was not necessary while other causes of endothelial injury were treated successfully.
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Affiliation(s)
- Ingo Kaczmarek
- Department of Cardiac Surgery, Ludwig-Maximilians-University, Grosshadern, Munich, Germany.
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