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Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review
Journal of Clinical Neuroscience xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review Alejandro Vargas a,⇑, Fernando D. Testai b a b
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL USA Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL USA
a r t i c l e
i n f o
Article history: Received 28 June 2019 Accepted 8 August 2019 Available online xxxx Keywords: Sickle-cell Adult Posterior Reversible Encephalopathy Syndrome PRES
a b s t r a c t Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by headache, seizures, confusion, and visual disturbance. Usual culprits include hypertension, eclampsia, renal failure, or immunosuppressants. PRES has been described in sickle cell patients on a case report basis. More often than not, the patients are children or a recent blood transfusion was culprit. Few case reports describe adults with PRES. We present a series of four adult sickle-cell patients who developed PRES. The association of hypertension, renal failure, and immunosuppressants in sickle cell patients may play a role in the development of PRES in this patient population. It is unclear if SC patients have a higher frequency of PRES predisposing factors than the general population or if SC is an independent risk factor for PRES. Despite this limitation, the presence of acute neurological status changes in adult SC patients should trigger suspicion for PRES as management and outcome may be altered. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by headache, seizures, confusion, and visual disturbance. Usual culprits include hypertension, eclampsia, renal failure, or immunosuppressants [1]. It has been rarely reported in adult sickle cell (SC) patients and this may stem from under-recognition due to common occurrence of neurological complaints in this patient population. We report a series of 4 cases of adult SC patients presenting with PRES. 2. Cases A 25-year-old female with SC disease, hypertension, renal failure, presented with seizure. She was hypertensive between systolic readings 180–200 mmHg. Magnetic resonance imaging (MRI) demonstrated T2 hyperintensities suggestive of PRES, which significantly improved on repeat imaging seven days later (Fig. 1A). A 34-year-old female with SC disease on chronic transfusions, hypertension, renal transplant on tacrolimus, presented with multiple seizures and blurred vision. She was hypertensive between systolic readings 188–200 mmHg and had not received a recent ⇑ Corresponding author at: Rush University Medical Center, Department of Neurological Sciences, 1725 W Harrison St. 1121, Chicago, IL 60612, USA. E-mail address: [email protected] (A. Vargas).
transfusion. MRI demonstrated multiple T2 hyperintensities suggestive of PRES (Fig. 1B). Her visual complaints resolved prior to discharge, and tacrolimus was replaced with cyclosporine. A 30-year-old male with SC disease and hypertension was admitted to an outside institution for a vaso-occlusive crisis, stabilized, and transferred a week later. He had a witnessed seizure while at our institution while relatively normotensive and MRI was suggestive of PRES. Repeat MRI 3 weeks later showed resolution of hyperintensities (Fig. 1C). A 32-year-old female with sickle cell disease with bone marrow transplant, on cyclosporine, was hypertensive with systolic readings 150–180 mmHg prior to sudden mental status change suggestive of seizures. MRI showed T2 abnormalities which resolved on repeat imaging 14 days later consistent with PRES (Fig. 1D).
3. Discussion PRES is typically seen in patients with severe hypertension, eclampsia, renal failure, or immunosuppression treatments [1,2]. PRES in SC is mainly reported in children or in association with recent blood transfusion or severe hypertension, rarely in adults [3]. One in this series has been previously reported in the literature as our institution benefits from a large SC population [4]. A comprehensive review of the reported cases of PRES in SC population was performed with the majority being pediatric patients [5].
https://doi.org/10.1016/j.jocn.2019.08.070 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: A. Vargas and F. D. Testai, Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.08.070
2
Case report / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. Magnetic Resonance Imaging findings of Posterior Reversible Encephalopathy Syndrome. T2 Fluid Attenuation Inversion Recovery (FLAIR) sequence demonstrating vasogenic edema on initial scan, and resolution on repeat examination from patient 1 (A), patient 2 (B), patient 3 (C), and patient 4 (D).
Most, however, are ten years of age or older, supportive of an adult phenomena [3]. The pathophysiology of PRES is theorized to be an endotheliopathy leading to failed cerebral autoregulation, edema, and encephalopathy [1]. Predilection for the posterior circulation might relate to relative lack of sympathetic innervation which is important to autoregulation. Hyperviscosity from sickled erythrocytes, ischemia, and chronic anemia may contribute to PRES in SC [5]. Hypoxia-induced nitric oxide and chemokine release with resultant vasodilation, endothelial dysfunction, and vasogenic edema may also play a role [5]. Transfusion alone has come to light as a possible trigger in patients with chronic anemia, from menorrhagia, iron deficiency anemia, or other hemoglobinopathy, but not reported in cases of acute blood loss such as trauma [5,6]. This suggests a chronic state of anemia is contributory. None of our cases occurred after transfusion, however, two of our four patients were on immunosuppressants and three of the four were hypertensive at presentation. The true prevalence of PRES may be underestimated in SC because mild symptoms may overlap with other etiologies (behavioral changes linked to opioid use during a pain crisis) [7]. It is important to distinguish the cause of a sudden neurological change in SC patients due to differences in acute management. For suspected acute ischemic stroke, permissive hypertension or exchange transfusion are commonly used, exacerbating PRES. Immediate MRI is warranted to confirm the diagnosis. The clinician’s suspicion should come into play as seizures, confusion, and headache are common symptoms in PRES but are vague and non-localizable. Repeat MRI in 2–4 weeks would be recommended to demonstrate reversibility. It is unclear if SC patients have a higher frequency of PRES predisposing factors (hypertension, renal failure, immunosuppressants, and transfusion) than the general population, SC may increase the risk with an inciting trigger, or if SC is an independent
risk factor for PRES. Despite this limitation and the higher exposure in pediatric populations, the presence of acute neurological status changes in adult SC patients should trigger suspicion for PRES as management and outcome may be altered. Declaration of Competing Interest Dr. Vargas and Dr. Testai report no conflict of interests or disclosures. No funding was received for this study. Appendix A. Supplementary material Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.08.070. References [1] Granata G, Greco A, Iannella G, et al. Posterior reversible encephalopathy syndrome–Insight into pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2015 Sep;14(9):830–6. [2] Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996 Feb 22;334(8):494–500. [3] Geevasinga N, Cole C, Herkes GK, Barnett Y, Lin J, Needham M. Sickle cell disease and posterior reversible leukoencephalopathy. J Clin Neurosci 2014 Aug;21 (8):1329–32. [4] Nair A, Testai FD. Recurrent posterior reversible encephalopathy syndrome in a sickle cell patient. J Natl Med Assoc 2011 Feb;103(2):170–2. [5] Solh Z, Taccone MS, Marin S, Athale U, Breakey VR. Neurological PRESentations in sickle cell patients are not always stroke: a review of posterior reversible encephalopathy syndrome in sickle cell disease. Pediatr Blood Cancer 2016 Jun;63(6):983–9. [6] Singh K, Gupta R, Kamal H, Silvestri NJ, Wolfe GI. Posterior reversible encephalopathy syndrome secondary to blood transfusion. J Clin Neurosci 2015 Mar;22(3):592–4. [7] Henderson JN, Noetzel JN, McKinstry RC, White DA, Armstrong M, DeBaun MR. Reversible posterior leukoencephalopathy syndrome and silent cerebral infarcts are associated with severe acute chest syndrome in children with sickle cell disease. Blood 2002;101:415–9.
Please cite this article as: A. Vargas and F. D. Testai, Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.08.070
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review Alejandro Vargas a,⇑, Fernando D. Testai b a b
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL USA Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL USA
a r t i c l e
i n f o
Article history: Received 28 June 2019 Accepted 8 August 2019 Available online xxxx Keywords: Sickle-cell Adult Posterior Reversible Encephalopathy Syndrome PRES
a b s t r a c t Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by headache, seizures, confusion, and visual disturbance. Usual culprits include hypertension, eclampsia, renal failure, or immunosuppressants. PRES has been described in sickle cell patients on a case report basis. More often than not, the patients are children or a recent blood transfusion was culprit. Few case reports describe adults with PRES. We present a series of four adult sickle-cell patients who developed PRES. The association of hypertension, renal failure, and immunosuppressants in sickle cell patients may play a role in the development of PRES in this patient population. It is unclear if SC patients have a higher frequency of PRES predisposing factors than the general population or if SC is an independent risk factor for PRES. Despite this limitation, the presence of acute neurological status changes in adult SC patients should trigger suspicion for PRES as management and outcome may be altered. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by headache, seizures, confusion, and visual disturbance. Usual culprits include hypertension, eclampsia, renal failure, or immunosuppressants [1]. It has been rarely reported in adult sickle cell (SC) patients and this may stem from under-recognition due to common occurrence of neurological complaints in this patient population. We report a series of 4 cases of adult SC patients presenting with PRES. 2. Cases A 25-year-old female with SC disease, hypertension, renal failure, presented with seizure. She was hypertensive between systolic readings 180–200 mmHg. Magnetic resonance imaging (MRI) demonstrated T2 hyperintensities suggestive of PRES, which significantly improved on repeat imaging seven days later (Fig. 1A). A 34-year-old female with SC disease on chronic transfusions, hypertension, renal transplant on tacrolimus, presented with multiple seizures and blurred vision. She was hypertensive between systolic readings 188–200 mmHg and had not received a recent ⇑ Corresponding author at: Rush University Medical Center, Department of Neurological Sciences, 1725 W Harrison St. 1121, Chicago, IL 60612, USA. E-mail address: [email protected] (A. Vargas).
transfusion. MRI demonstrated multiple T2 hyperintensities suggestive of PRES (Fig. 1B). Her visual complaints resolved prior to discharge, and tacrolimus was replaced with cyclosporine. A 30-year-old male with SC disease and hypertension was admitted to an outside institution for a vaso-occlusive crisis, stabilized, and transferred a week later. He had a witnessed seizure while at our institution while relatively normotensive and MRI was suggestive of PRES. Repeat MRI 3 weeks later showed resolution of hyperintensities (Fig. 1C). A 32-year-old female with sickle cell disease with bone marrow transplant, on cyclosporine, was hypertensive with systolic readings 150–180 mmHg prior to sudden mental status change suggestive of seizures. MRI showed T2 abnormalities which resolved on repeat imaging 14 days later consistent with PRES (Fig. 1D).
3. Discussion PRES is typically seen in patients with severe hypertension, eclampsia, renal failure, or immunosuppression treatments [1,2]. PRES in SC is mainly reported in children or in association with recent blood transfusion or severe hypertension, rarely in adults [3]. One in this series has been previously reported in the literature as our institution benefits from a large SC population [4]. A comprehensive review of the reported cases of PRES in SC population was performed with the majority being pediatric patients [5].
https://doi.org/10.1016/j.jocn.2019.08.070 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: A. Vargas and F. D. Testai, Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.08.070
2
Case report / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. Magnetic Resonance Imaging findings of Posterior Reversible Encephalopathy Syndrome. T2 Fluid Attenuation Inversion Recovery (FLAIR) sequence demonstrating vasogenic edema on initial scan, and resolution on repeat examination from patient 1 (A), patient 2 (B), patient 3 (C), and patient 4 (D).
Most, however, are ten years of age or older, supportive of an adult phenomena [3]. The pathophysiology of PRES is theorized to be an endotheliopathy leading to failed cerebral autoregulation, edema, and encephalopathy [1]. Predilection for the posterior circulation might relate to relative lack of sympathetic innervation which is important to autoregulation. Hyperviscosity from sickled erythrocytes, ischemia, and chronic anemia may contribute to PRES in SC [5]. Hypoxia-induced nitric oxide and chemokine release with resultant vasodilation, endothelial dysfunction, and vasogenic edema may also play a role [5]. Transfusion alone has come to light as a possible trigger in patients with chronic anemia, from menorrhagia, iron deficiency anemia, or other hemoglobinopathy, but not reported in cases of acute blood loss such as trauma [5,6]. This suggests a chronic state of anemia is contributory. None of our cases occurred after transfusion, however, two of our four patients were on immunosuppressants and three of the four were hypertensive at presentation. The true prevalence of PRES may be underestimated in SC because mild symptoms may overlap with other etiologies (behavioral changes linked to opioid use during a pain crisis) [7]. It is important to distinguish the cause of a sudden neurological change in SC patients due to differences in acute management. For suspected acute ischemic stroke, permissive hypertension or exchange transfusion are commonly used, exacerbating PRES. Immediate MRI is warranted to confirm the diagnosis. The clinician’s suspicion should come into play as seizures, confusion, and headache are common symptoms in PRES but are vague and non-localizable. Repeat MRI in 2–4 weeks would be recommended to demonstrate reversibility. It is unclear if SC patients have a higher frequency of PRES predisposing factors (hypertension, renal failure, immunosuppressants, and transfusion) than the general population, SC may increase the risk with an inciting trigger, or if SC is an independent
risk factor for PRES. Despite this limitation and the higher exposure in pediatric populations, the presence of acute neurological status changes in adult SC patients should trigger suspicion for PRES as management and outcome may be altered. Declaration of Competing Interest Dr. Vargas and Dr. Testai report no conflict of interests or disclosures. No funding was received for this study. Appendix A. Supplementary material Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.08.070. References [1] Granata G, Greco A, Iannella G, et al. Posterior reversible encephalopathy syndrome–Insight into pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2015 Sep;14(9):830–6. [2] Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996 Feb 22;334(8):494–500. [3] Geevasinga N, Cole C, Herkes GK, Barnett Y, Lin J, Needham M. Sickle cell disease and posterior reversible leukoencephalopathy. J Clin Neurosci 2014 Aug;21 (8):1329–32. [4] Nair A, Testai FD. Recurrent posterior reversible encephalopathy syndrome in a sickle cell patient. J Natl Med Assoc 2011 Feb;103(2):170–2. [5] Solh Z, Taccone MS, Marin S, Athale U, Breakey VR. Neurological PRESentations in sickle cell patients are not always stroke: a review of posterior reversible encephalopathy syndrome in sickle cell disease. Pediatr Blood Cancer 2016 Jun;63(6):983–9. [6] Singh K, Gupta R, Kamal H, Silvestri NJ, Wolfe GI. Posterior reversible encephalopathy syndrome secondary to blood transfusion. J Clin Neurosci 2015 Mar;22(3):592–4. [7] Henderson JN, Noetzel JN, McKinstry RC, White DA, Armstrong M, DeBaun MR. Reversible posterior leukoencephalopathy syndrome and silent cerebral infarcts are associated with severe acute chest syndrome in children with sickle cell disease. Blood 2002;101:415–9.
Please cite this article as: A. Vargas and F. D. Testai, Posterior Reversible Encephalopathy Syndrome in adult sickle-cell patients: Case series and literature review, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.08.070