American Journal of Transplantation 2015; 15: 823–826 Wiley Periodicals Inc.
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Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13021
Case Report
A Unique Case of Rituximab-Related Posterior Reversible Encephalopathy Syndrome in a Heart Transplant Recipient With Posttransplant Lymphoproliferative Disorder A. Jaiswal1, I. Sabnani2, D. A. Baran3 and M. J. Zucker3,* 1
Tulane University Heart and Vascular Institute, New Orleans, LA 2 Division of Hematology and Oncology, Department of Medicine, Newark Beth Israel Medical Center, Newark, NJ 3 Heart Failure Treatment, Cardiac Transplant Center, Newark Beth Israel Medical Center, Newark, NJ Corresponding author: Mark J. Zucker, [email protected]
Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients. Abbreviations: CMV, cytomegalovirus; CT, computed tomography; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; PRES, posterior reversible encephalopathy syndrome; PTLD, posttransplant lymphoproliferative diseases; T2W, T2-weighted MRI protocol Received 10 July 2014, revised 04 September 2014 and accepted for publication 06 September 2014
Introduction Posterior reversible encephalopathy or leukoencephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by alteration in mental status (confusion and stupor), headaches, visual disturbances and seizures accompanied by distinctive magnetic resonance imaging (MRI) findings of diffuse cortical and subcortical white matter signal abnormality (1). These radiological abnormalities are usually seen in a symmetric bilateral distribution involving mainly the parietal and occipital lobes and result from vasogenic edema (2). The syndrome was first reported by Hinchey et al (3) and was felt to be mostly associated with acute hypertension, renal failure, eclampsia, sepsis and immunosuppressive therapy. As MRI became more widely available the frequency with which PRES is diagnosed increased as well. Today, PRES is identified most frequently in patients being treated with various chemotherapeutic or immunomodulatory agents and in patients with partially compromised immune function due to chronic illness such as may occur in rheumatologic diseases (4–6). Some cases have been described after solid organ transplantation and after the administration of rituximab (7–10), however, there are no case reports describing the development of PRES in heart transplant recipients receiving rituximab for treatment of posttransplant lymphoproliferative disorder (PTLD). We describe an interesting case of heart transplant recipient who developed PRES after being treated with rituximab for PTLD.
Case Report A 45-year-old man who underwent heart transplant 9 years prior for underlying dilated cardiomyopathy reported fever, night sweats, diarrhea and lymphadenopathy for a couple of weeks. A lymph node biopsy confirmed the diagnosis of diffuse large B-cell lymphoma with CD 20 positive large atypical lymphocytes. The patient was treated with six cycles of R-CHOP (rituximab, adriamycin, cyclophosphamide, vincristine, prednisone) chemotherapy with modified doses of adriamycin and cyclophosphamide in view of the underlying heart transplant and calcineurin-associated renal insufficiency with baseline serum creatinine around 823
Jaiswal et al
4.0 mg/dL. The patient remained in remission for a total duration of 9 months after treatment. After relapse, salvage therapy for Stage IIB PTLD was begun using carboplatin, etoposide and rituximab. On day 8 of the second cycle of chemotherapy, the patient presented with headaches, confusion, blurry vision and behavioral changes. A CT scan of brain was performed and was reportedly unremarkable. Symptoms resolved with symptomatic treatment over a period of few days. Similarly, on Day 8 of the third cycle of chemotherapy, the patient again developed neurological symptoms including cortical blindness and hallucinations. This time, however, rather than a CT scan, a contrast MRI of brain was performed, which showed fairly symmetric areas of abnormal increased signal intensity in the subcortical white matter of the occipital lobes bilaterally on both the FLAIR and T2W sequences (Figure 1). Spinal fluid examination was normal and was negative for JC polyoma virus. The neurological symptoms and MRI findings resolved over a period of 7–10 days with complete recovery of visual acuity (Figure 2). During fourth cycle of chemotherapy, rituximab was withheld and no neurological symptoms developed. He now remains in complete remission without any residual neurological deficit more than 60 months after completing the course of salvage therapy.
Discussion Posterior reversible encephalopathy syndrome or PRES is characterized by a combination of neurological symptoms and radiological findings suggestive of reversible intracranial vasogenic edema. The clinical presentation may include headache, visual disturbance, personality changes, altered
mental status and seizures. The classic radiological changes consist of bilateral symmetrical vasogenic edema predominantly affecting the parieto-occipital region (1). These findings are best demonstrated as a hyperintense signal on FLAIR (Fluid Attenuated Inversion Recovery) sequence of T2 MRI scanning (2). Proton MRI spectroscopy (H-MRS) might show mild increase in choline (Cho) and creatinine (Cr) peaks with mild decrease in n-acetyl aspartate (NAA) peaks without reversal of angle (11). The pathophysiology of PRES is not fully understood but is believed to be related to breakdown in cerebral autoregulation leading to hyperperfusion, protein and fluid extravasation and endothelial dysfunction causing edema, vasospasm and ischemia (12). There is an increased predisposition for posterior circulation distribution involvement perhaps due to the lack of sympathetic innervation (13). The PRES is commonly attributed to acute hypertension, uremia, eclampsia, sepsis and immunosuppressive agents such as cyclosporine and tacrolimus (3,4). In addition to immunosuppressive therapy, cytotoxic drugs like dexamethasone, carboplatin, gemcitabine and bevacizumab have also been reported as causative agents (8–10). Recently, there have been reports of rituximab-related PRES in patients with underlying lupus or rheumatoid arthritis (6). Likewise, immunocompromised patients such as those after solid organ or bone marrow transplantation are also at a higher risk of developing PRES. In a retrospective study of over 4,000 kidney, heart, lung, liver pancreas and bowel transplant recipients, the incidence of PRES was found to be 0.4% (7). While the authors offered no specific conclusions regarding precipitating factors in thoracic organ recipients (probably due to the relatively small population of affected thoracic organ recipients—5 out of a total of 791 heart and/or lung transplant patients),
Figure 1: Magnetic resonance imaging (MRI) scan with FLAIR (on left panel) and post contrast study (on right panel) showing abnormal increased intensity in occipital lobe subcortical white matter changes with scattered parietal lobe changes.
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American Journal of Transplantation 2015; 15: 823–826
Rituximab Related PRES in PTLD
Figure 2: Follow-up MRI scan with FLAIR (on left panel) and postcontrast study (on right panel) showing resolution of occipital lobe subcortical white matter changes.
when the entire cohort was looked at as a whole, the development of PRES seemed to occur most commonly in association with bacterial infections, CMV infection and organ rejection. Headache, visual disturbances and seizures in a chemotherapy patient with malignant disease includes broad differential diagnosis such as subarachnoid hemorrhage, primary or secondary malignancy in brain, infections, stroke, side effects of chemotherapeutic agents, metabolic disorders due to tumor lysis syndrome and PRES. Our patient, the only heart transplant recipient at our institution to develop this syndrome (out of a total of 600 recipients) presented with typical clinical symptoms of hallucination, cortical blindness, headaches and behavioral changes associated with classical radiological findings on MRI, in the absence of high blood pressure, metabolic derangements, infection or rejection. The strong indirect evidence of rituximab related PRES in our patient is suggested by the fact that there were no neurological symptoms, once rituximab was discontinued during the fourth cycle of therapy. Rituximab, a monoclonal antibody against CD20, is widely used in various hematological malignancies, systemic lupus erythematosus, neuromyelitis optica and sarcoidosis, and because of the expression of CD20 in activated endothelial cells, it may cause direct cell damage and endothelin mediated vasospasm (14,15). In the era of increasing use of rituximab as the front line therapy for PTLD and in refractory antibody mediated graft rejection, immunocompromised transplant recipients may be more susceptible to the development of PRES. Clinicians should be aware of this generally unrecognized complication while using rituximab for the management of PTLD and or antibody mediated graft rejection (16) in solid organ transplant recipients. American Journal of Transplantation 2015; 15: 823–826
Although our patient had multiple underlying predisposing factors for development of PRES (chronic hypertension, renal insufficiency, tacrolimus), at the time of presentation there was no evidence of uncontrolled hypertension, infection, tacrolimus toxicity or rejection as has been described in other series. The temporal relationship between the development of PRES after the second and third cycles of chemotherapy but the absence of symptoms after removing rituximab from the fourth cycle of chemotherapy strongly suggests that rituximab was the causative agent in our immunocompromised patient. PRES is usually reversible by removing the inciting agent or the hypertension management. Nevertheless, early recognition is essential as delay may lead to status epilepticus, intracranial hemorrhage, ischemic infarction leading to permanent neurologic damage or death (17–19). Management of PRES requires immediate institution of symptomatic treatment along with correction of known inciting factors—blood pressure control, infection treatment, dialysis and removal of toxic agents. Patient should be promptly transferred to intensive care unit (ICU) for close hemodynamic and neurological monitoring. The ICU care should include early recognition and prompt correction of hypoglycemia, hyperthermia, hyperkalemia and hypomagnesemia. Treatment of seizure should be initiated as per current guidelines, appropriate for clinical and electrical pattern. If present, hypertensive emergency should be immediately managed as per current guidelines (20). One should never aim to normalize blood pressure acutely as rapid/precipitous drop can lead to cerebral ischemia. Our patient was treated symptomatically and showed complete resolution of symptoms within 7–10 days. A follow-up MRI also revealed resolution of previous edema and cortical abnormalities. In addition to being the first case 825
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report of rituximab related PRES in a patient with PTLD in a heart transplant recipient this interesting case also provides some other unique features. First, in this case PRES did not develop after the first dose of rituximab, a finding, which has not been previously reported. Second, most likely our case had PRES events twice. During the first episode we opted for CT scan instead of an MRI scan due to the higher suspicion of stroke. Third, we report a follow-up of more than 60 months, which has never been reported before. To conclude, clinicians should always be on alert when using rituximab in high-risk patient populations such as transplant recipients with PTLD or antibody mediated graft rejection. The heightened awareness, early identification and resolution of the underlying cause remain the cornerstones of management to prevent irreversible and potentially fatal complications associated with PRES.
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol 2001; 24: 361– 364. 2. Lamy C, Oppenheim C, Me´der JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging 2004; 14: 89–96. 3. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494– 500. 4. Parvex P, Pinsk M, Bell LE, O’Gorman AM, Patenaude YG, Gupta IR. Reversible encephalopathy associated with tacrolimus in pediatric renal transplants. Pediatr Nephrol 2001; 16: 537–542. 5. Tam CS, Galanos J, Seymour JF, Pitman AG, Stark RJ, Prince HM. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004; 77: 72–76.
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6. Kur JK, Esdaile JM. Posterior reversible encephalopathy syndrome—An underrecognized manifestation of systemic lupus erythematosus. J Rheumatol 2006; 33: 2178–2183. 7. Bartynski WS, Tan HP, Boardman JF, Shapiro R, Marsh JW. Posterior reversible encephalopathy syndrome after solid organ transplantation. Am J Neuroradiol 2008; 29: 924–930. 8. Vieillot S, Pouessel D, de Champfleur NM, Becht C, Culine S. Reversible posterior leukoencephalopathy syndrome after carboplatin therapy. Ann Oncol 2007; 18: 608–609. 9. Irvin W, MacDonald G, Smith JK, Kim WY. Dexamethasoneinduced posterior reversible encephalopathy syndrome. J Clin Oncol 2007; 25: 2484–2486. 10. Allen JA, Adlakha A, Bergethon PR. Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer. Arch Neurol 2006; 63: 1475–1478. 11. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: Fundamental imaging and clinical features. Am J Neuroradiol 2008; 29: 1036–1042. 12. Port JD, Beauchamp NJ Jr. Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 1998; 18: 353–367. 13. McKinney AM, Short J, Truwit CL, et al. Posterior reversible encephalopathy syndrome: Incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007; 189: 904–912. 14. Sa´nchez-Carteyron A, Alarcia R, Ara JR, Martı´n J. Posterior reversible encephalopathy syndrome after rituximab infusion in neuromyelitis optica. Neurology 2010; 74: 1471–1473. 15. Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med J 2001; 77: 24–28. 16. Blume OR, Yost SE, Kaplan B. Antibody-mediated rejection: Pathogenesis, prevention, treatment, and outcomes. J Transplant 2012; 2012: 201754. 17. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: A misnomer reviewed. Intern Med J 2005; 35: 83–90. 18. Kwon J, Kim S, Kim K, et al. A case of gemcitabine and cisplatin associated posterior reversible encephalopathy syndrome. Cancer Treat Res 2009; 41: 53–55. 19. Ay H, Buonanno FS, Schaefer PW, et al. Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI. Neurology 1998; 51: 1369–1376. 20. Zaidi G, Chichra A, Weitzen M, et al. Blood pressure control in neurological ICU patients: What is too high and what is too low? Open Crit Care Med J 2013; 6: 46–55.
American Journal of Transplantation 2015; 15: 823–826
Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
C
Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13021
Case Report
A Unique Case of Rituximab-Related Posterior Reversible Encephalopathy Syndrome in a Heart Transplant Recipient With Posttransplant Lymphoproliferative Disorder A. Jaiswal1, I. Sabnani2, D. A. Baran3 and M. J. Zucker3,* 1
Tulane University Heart and Vascular Institute, New Orleans, LA 2 Division of Hematology and Oncology, Department of Medicine, Newark Beth Israel Medical Center, Newark, NJ 3 Heart Failure Treatment, Cardiac Transplant Center, Newark Beth Israel Medical Center, Newark, NJ Corresponding author: Mark J. Zucker, [email protected]
Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients. Abbreviations: CMV, cytomegalovirus; CT, computed tomography; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; PRES, posterior reversible encephalopathy syndrome; PTLD, posttransplant lymphoproliferative diseases; T2W, T2-weighted MRI protocol Received 10 July 2014, revised 04 September 2014 and accepted for publication 06 September 2014
Introduction Posterior reversible encephalopathy or leukoencephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by alteration in mental status (confusion and stupor), headaches, visual disturbances and seizures accompanied by distinctive magnetic resonance imaging (MRI) findings of diffuse cortical and subcortical white matter signal abnormality (1). These radiological abnormalities are usually seen in a symmetric bilateral distribution involving mainly the parietal and occipital lobes and result from vasogenic edema (2). The syndrome was first reported by Hinchey et al (3) and was felt to be mostly associated with acute hypertension, renal failure, eclampsia, sepsis and immunosuppressive therapy. As MRI became more widely available the frequency with which PRES is diagnosed increased as well. Today, PRES is identified most frequently in patients being treated with various chemotherapeutic or immunomodulatory agents and in patients with partially compromised immune function due to chronic illness such as may occur in rheumatologic diseases (4–6). Some cases have been described after solid organ transplantation and after the administration of rituximab (7–10), however, there are no case reports describing the development of PRES in heart transplant recipients receiving rituximab for treatment of posttransplant lymphoproliferative disorder (PTLD). We describe an interesting case of heart transplant recipient who developed PRES after being treated with rituximab for PTLD.
Case Report A 45-year-old man who underwent heart transplant 9 years prior for underlying dilated cardiomyopathy reported fever, night sweats, diarrhea and lymphadenopathy for a couple of weeks. A lymph node biopsy confirmed the diagnosis of diffuse large B-cell lymphoma with CD 20 positive large atypical lymphocytes. The patient was treated with six cycles of R-CHOP (rituximab, adriamycin, cyclophosphamide, vincristine, prednisone) chemotherapy with modified doses of adriamycin and cyclophosphamide in view of the underlying heart transplant and calcineurin-associated renal insufficiency with baseline serum creatinine around 823
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4.0 mg/dL. The patient remained in remission for a total duration of 9 months after treatment. After relapse, salvage therapy for Stage IIB PTLD was begun using carboplatin, etoposide and rituximab. On day 8 of the second cycle of chemotherapy, the patient presented with headaches, confusion, blurry vision and behavioral changes. A CT scan of brain was performed and was reportedly unremarkable. Symptoms resolved with symptomatic treatment over a period of few days. Similarly, on Day 8 of the third cycle of chemotherapy, the patient again developed neurological symptoms including cortical blindness and hallucinations. This time, however, rather than a CT scan, a contrast MRI of brain was performed, which showed fairly symmetric areas of abnormal increased signal intensity in the subcortical white matter of the occipital lobes bilaterally on both the FLAIR and T2W sequences (Figure 1). Spinal fluid examination was normal and was negative for JC polyoma virus. The neurological symptoms and MRI findings resolved over a period of 7–10 days with complete recovery of visual acuity (Figure 2). During fourth cycle of chemotherapy, rituximab was withheld and no neurological symptoms developed. He now remains in complete remission without any residual neurological deficit more than 60 months after completing the course of salvage therapy.
Discussion Posterior reversible encephalopathy syndrome or PRES is characterized by a combination of neurological symptoms and radiological findings suggestive of reversible intracranial vasogenic edema. The clinical presentation may include headache, visual disturbance, personality changes, altered
mental status and seizures. The classic radiological changes consist of bilateral symmetrical vasogenic edema predominantly affecting the parieto-occipital region (1). These findings are best demonstrated as a hyperintense signal on FLAIR (Fluid Attenuated Inversion Recovery) sequence of T2 MRI scanning (2). Proton MRI spectroscopy (H-MRS) might show mild increase in choline (Cho) and creatinine (Cr) peaks with mild decrease in n-acetyl aspartate (NAA) peaks without reversal of angle (11). The pathophysiology of PRES is not fully understood but is believed to be related to breakdown in cerebral autoregulation leading to hyperperfusion, protein and fluid extravasation and endothelial dysfunction causing edema, vasospasm and ischemia (12). There is an increased predisposition for posterior circulation distribution involvement perhaps due to the lack of sympathetic innervation (13). The PRES is commonly attributed to acute hypertension, uremia, eclampsia, sepsis and immunosuppressive agents such as cyclosporine and tacrolimus (3,4). In addition to immunosuppressive therapy, cytotoxic drugs like dexamethasone, carboplatin, gemcitabine and bevacizumab have also been reported as causative agents (8–10). Recently, there have been reports of rituximab-related PRES in patients with underlying lupus or rheumatoid arthritis (6). Likewise, immunocompromised patients such as those after solid organ or bone marrow transplantation are also at a higher risk of developing PRES. In a retrospective study of over 4,000 kidney, heart, lung, liver pancreas and bowel transplant recipients, the incidence of PRES was found to be 0.4% (7). While the authors offered no specific conclusions regarding precipitating factors in thoracic organ recipients (probably due to the relatively small population of affected thoracic organ recipients—5 out of a total of 791 heart and/or lung transplant patients),
Figure 1: Magnetic resonance imaging (MRI) scan with FLAIR (on left panel) and post contrast study (on right panel) showing abnormal increased intensity in occipital lobe subcortical white matter changes with scattered parietal lobe changes.
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American Journal of Transplantation 2015; 15: 823–826
Rituximab Related PRES in PTLD
Figure 2: Follow-up MRI scan with FLAIR (on left panel) and postcontrast study (on right panel) showing resolution of occipital lobe subcortical white matter changes.
when the entire cohort was looked at as a whole, the development of PRES seemed to occur most commonly in association with bacterial infections, CMV infection and organ rejection. Headache, visual disturbances and seizures in a chemotherapy patient with malignant disease includes broad differential diagnosis such as subarachnoid hemorrhage, primary or secondary malignancy in brain, infections, stroke, side effects of chemotherapeutic agents, metabolic disorders due to tumor lysis syndrome and PRES. Our patient, the only heart transplant recipient at our institution to develop this syndrome (out of a total of 600 recipients) presented with typical clinical symptoms of hallucination, cortical blindness, headaches and behavioral changes associated with classical radiological findings on MRI, in the absence of high blood pressure, metabolic derangements, infection or rejection. The strong indirect evidence of rituximab related PRES in our patient is suggested by the fact that there were no neurological symptoms, once rituximab was discontinued during the fourth cycle of therapy. Rituximab, a monoclonal antibody against CD20, is widely used in various hematological malignancies, systemic lupus erythematosus, neuromyelitis optica and sarcoidosis, and because of the expression of CD20 in activated endothelial cells, it may cause direct cell damage and endothelin mediated vasospasm (14,15). In the era of increasing use of rituximab as the front line therapy for PTLD and in refractory antibody mediated graft rejection, immunocompromised transplant recipients may be more susceptible to the development of PRES. Clinicians should be aware of this generally unrecognized complication while using rituximab for the management of PTLD and or antibody mediated graft rejection (16) in solid organ transplant recipients. American Journal of Transplantation 2015; 15: 823–826
Although our patient had multiple underlying predisposing factors for development of PRES (chronic hypertension, renal insufficiency, tacrolimus), at the time of presentation there was no evidence of uncontrolled hypertension, infection, tacrolimus toxicity or rejection as has been described in other series. The temporal relationship between the development of PRES after the second and third cycles of chemotherapy but the absence of symptoms after removing rituximab from the fourth cycle of chemotherapy strongly suggests that rituximab was the causative agent in our immunocompromised patient. PRES is usually reversible by removing the inciting agent or the hypertension management. Nevertheless, early recognition is essential as delay may lead to status epilepticus, intracranial hemorrhage, ischemic infarction leading to permanent neurologic damage or death (17–19). Management of PRES requires immediate institution of symptomatic treatment along with correction of known inciting factors—blood pressure control, infection treatment, dialysis and removal of toxic agents. Patient should be promptly transferred to intensive care unit (ICU) for close hemodynamic and neurological monitoring. The ICU care should include early recognition and prompt correction of hypoglycemia, hyperthermia, hyperkalemia and hypomagnesemia. Treatment of seizure should be initiated as per current guidelines, appropriate for clinical and electrical pattern. If present, hypertensive emergency should be immediately managed as per current guidelines (20). One should never aim to normalize blood pressure acutely as rapid/precipitous drop can lead to cerebral ischemia. Our patient was treated symptomatically and showed complete resolution of symptoms within 7–10 days. A follow-up MRI also revealed resolution of previous edema and cortical abnormalities. In addition to being the first case 825
Jaiswal et al
report of rituximab related PRES in a patient with PTLD in a heart transplant recipient this interesting case also provides some other unique features. First, in this case PRES did not develop after the first dose of rituximab, a finding, which has not been previously reported. Second, most likely our case had PRES events twice. During the first episode we opted for CT scan instead of an MRI scan due to the higher suspicion of stroke. Third, we report a follow-up of more than 60 months, which has never been reported before. To conclude, clinicians should always be on alert when using rituximab in high-risk patient populations such as transplant recipients with PTLD or antibody mediated graft rejection. The heightened awareness, early identification and resolution of the underlying cause remain the cornerstones of management to prevent irreversible and potentially fatal complications associated with PRES.
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol 2001; 24: 361– 364. 2. Lamy C, Oppenheim C, Me´der JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging 2004; 14: 89–96. 3. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494– 500. 4. Parvex P, Pinsk M, Bell LE, O’Gorman AM, Patenaude YG, Gupta IR. Reversible encephalopathy associated with tacrolimus in pediatric renal transplants. Pediatr Nephrol 2001; 16: 537–542. 5. Tam CS, Galanos J, Seymour JF, Pitman AG, Stark RJ, Prince HM. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004; 77: 72–76.
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6. Kur JK, Esdaile JM. Posterior reversible encephalopathy syndrome—An underrecognized manifestation of systemic lupus erythematosus. J Rheumatol 2006; 33: 2178–2183. 7. Bartynski WS, Tan HP, Boardman JF, Shapiro R, Marsh JW. Posterior reversible encephalopathy syndrome after solid organ transplantation. Am J Neuroradiol 2008; 29: 924–930. 8. Vieillot S, Pouessel D, de Champfleur NM, Becht C, Culine S. Reversible posterior leukoencephalopathy syndrome after carboplatin therapy. Ann Oncol 2007; 18: 608–609. 9. Irvin W, MacDonald G, Smith JK, Kim WY. Dexamethasoneinduced posterior reversible encephalopathy syndrome. J Clin Oncol 2007; 25: 2484–2486. 10. Allen JA, Adlakha A, Bergethon PR. Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer. Arch Neurol 2006; 63: 1475–1478. 11. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: Fundamental imaging and clinical features. Am J Neuroradiol 2008; 29: 1036–1042. 12. Port JD, Beauchamp NJ Jr. Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 1998; 18: 353–367. 13. McKinney AM, Short J, Truwit CL, et al. Posterior reversible encephalopathy syndrome: Incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007; 189: 904–912. 14. Sa´nchez-Carteyron A, Alarcia R, Ara JR, Martı´n J. Posterior reversible encephalopathy syndrome after rituximab infusion in neuromyelitis optica. Neurology 2010; 74: 1471–1473. 15. Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med J 2001; 77: 24–28. 16. Blume OR, Yost SE, Kaplan B. Antibody-mediated rejection: Pathogenesis, prevention, treatment, and outcomes. J Transplant 2012; 2012: 201754. 17. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: A misnomer reviewed. Intern Med J 2005; 35: 83–90. 18. Kwon J, Kim S, Kim K, et al. A case of gemcitabine and cisplatin associated posterior reversible encephalopathy syndrome. Cancer Treat Res 2009; 41: 53–55. 19. Ay H, Buonanno FS, Schaefer PW, et al. Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI. Neurology 1998; 51: 1369–1376. 20. Zaidi G, Chichra A, Weitzen M, et al. Blood pressure control in neurological ICU patients: What is too high and what is too low? Open Crit Care Med J 2013; 6: 46–55.
American Journal of Transplantation 2015; 15: 823–826
Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
