Objectives: In this study, we presented neuroradiologic findings and diagnoses of neurologic complications in a series of heart transplant recipients.

Materials and Methods: A retrospective review was conducted at Başkent University Hospital. We searched the hospital and radiology databases and identified 109 heart transplant recipients. Thirty-one of these recipients had neuroradiologic evaluations secondary to presentation of neurologic symptoms after heart transplant, with 18 patients evaluated with computed tomography and 22 patients evaluated with magnetic resonance imaging (overlap of imaging-defined groups occurred in 9 recipients). Computed tomog­raphy and magnetic resonance imaging studies were retrieved from the Picture Archiving and Communication System, with each type of imaging retrospectively evaluated on consensus by 2 radiologists.

Results: Radiopathologic findings related to symptoms were detected in 12 of the 31 study patients. The most common abnormality was posterior reversible leuko­encephalopathy syndrome (5 patients, 4.6%). The other abnormalities were ischemic stroke (3 patients, 2.8%), hemorrhagic stroke (1 patient, 0.9%), intracranial abscess (2 patients, 1.8%), and intracranial dissem­ination of sinusoidal fungal infection and related hemorrhagic infarct (1 patient, 0.9%). The other 19 heart transplant recipients who underwent computed tomography and/or magnetic resonance imaging for neurologic complaints showed no neuroradiologic findings related to neurologic symptoms.

Conclusions: Posterior reversible leukoencephalopathy syndrome and ischemic stroke were the most common neurologic complications in our heart transplant recipients. The other complications were hemorrhagic stroke, intracranial abscess, and intracranial dis­semination of sinusoidal fungal infection. Neurologic complications are common in heart transplant recipients and should be identified promptly for early treatment. For the recognition of these complications, computed tomography should be performed for initial evaluation to rule out edema or hemorrhage. However, in the presence of serious neurologic symptoms that cannot be explained by computed tomography, magnetic resonance imaging should be indicated.

Key words : Heart transplantation, Neurologic complications, PRES, Stroke

Introduction

Currently, heart transplantation remains the best long-term therapy for patients with end-stage heart failure who have failed conventional medical therapies.¹ Patients who are candidates for heart transplant have an increased prevalence of vascular risk factors, such as hypertension, hypercho­lesterolemia, diabetes, obesity, and smoking. As a result, neurologic complications occur more commonly with heart transplant compared with other transplant procedures.² Frequency of these complications depends on follow-up, ranging from 23% to 81%. Ischemic stroke is the most common cerebrovascular complication in heart transplant recipients.^1,3 Posterior reversible leukoencephalopathy syndrome (PRES) is another common neurologic complication in these patients. Other early and late cerebrovascular complications include hemorrhagic stroke, transient ischemic attack, and less often central nervous system (CNS) infections, mass, and lymphoproliferative disorders.^1,4,5

Neurologic complications are associated with significant morbidity and increased mortality in heart transplant recipients.³ The clinical presentation ranges from generalized encephalopathy to focal neurologic deficits,^3,6 but the diagnosis is often difficult because systemic and metabolic disorders and immunosuppressive therapy may obscure symptoms of an underlying CNS lesion.^7,8 Prompt neuroradiologic diagnosis is crucial for the proper treatment of serious neurologic complications. The role of neuroradiology in this population includes the early detection and monitoring of the progression of complications, evaluation of treatment response, and localization of the appropriate site for stereotactic or open biopsy in specific cases.^9,10 Brain computed tomography (CT) and/or magnetic resonance imaging (MRI) studies are often necessary after the clinical examination and electrodiagnostic and laboratory tests when neurologic symptoms present in heart transplant recipients. In this study, we reviewed the neuroradiologic findings and diagnoses of neurologic complications in a series of heart transplant recipients.

Materials and Methods

A retrospective review was conducted on all patients who underwent heart transplantation at Başkent University Hospital. Institutional review board approval was obtained before the study. We searched the hospital and radiology databases and identified 109 heart transplant recipients. Of these, 31 recipients received neuroradiologic evaluation secondary to presentation of neurologic symptoms after heart transplant. These symptoms were evaluated with CT in 18 recipients and with MRI in 22 recipients (with overlap of imaging-defined groups in 9 recipients). These 31 patients made up our study group.

Demographic and clinical factors, such as age, sex, reason for transplant, symptoms at time of presentation, time from transplant to onset of symptoms, physical findings, medications, and additional diseases of recipients, were recorded.

Computed tomography scans were performed using 4-detector CT (Somatom 4; Siemens, Erlangen, Germany) or 16-detector CT (Sensation 16; Siemens). With 16- or 4- detector CT, images were obtained at a 3- or 2.5-mm slice thickness for the posterior fossa and a 5- or 6-mm slice thickness for the supra­tentorial region. Contrast medium was administered in patients when needed.

Magnetic resonance imaging studies were performed on a Siemens 1.5T (Magnetom Avanto, Erlangen, Germany) system. In all patients, T1-weighted axial and sagittal images (time of repetition [TR]/time of echo [TE]/number of excitations [NEX]/slice thickness = 500-580/13-15/2/5-5.5), T2-weighted coronal images (TR/TE/NEX/slice thickness = 4100-5160/99-103/2/5-5.5), and fluid-attenuated inversion recovery axial images (TR/TE/NEX/slice thickness = 9000-10 000/105-140/2/5-5.5) were acquired. Echo planar images were obtained with diffusion gradients at 1.5T in x, y, and z planes using 5-mm-thick sections with 1.5 mm of skip at b = 0, 500, and 1000 s/mm2. Apparent diffusion coefficient maps were automatically generated. T1-weighted images in axial and coronal planes were obtained after intravenous gadolinium administration (0.1 mmol/kg) in patients with possible abscess or encephalitis. Patients were sedated when needed; these patients were monitored by electrocardiography and pulse oximetry with an anesthesiologist present throughout the examination.

Images of CT and MRI studies were retrieved from the Picture Archiving and Communication System and were retrospectively evaluated on consensus by 2 radiologists.

Results

In the 31 heart transplant recipients who underwent CT and/or MRI, mean age at the onset of symptoms was 30.4 years (range, 7.5-59 y). The patient group consisted of 16 male (51.6%) and 15 female (48.4%) heart transplant recipients. Overall time from transplant to onset of symptoms was 3 days to 7 years (mean of 15.5 mo). Underlying diseases that had resulted in heart failure varied widely. Causes of heart failure in the 31 study patients are shown in Table 1. All patients were under mycophenolate mofetil (a selective immunosuppressant agent) and/or tacrolimus (a calcineurin inhibitor) and/or prednisolone (a systemic corticosteroid) therapy.

Patients presented with various symptoms. Two patients were evaluated for possible metastasis and aspergillosis, although they did not have any symptoms. Details of the indications for CT and/or MRI examinations are shown in Table 2.

Radiopathologic findings related to symptoms were detected in 12 of the 31 heart transplant recipients who underwent CT and/or MRI. The diagnosis, symptoms, and time from transplant to onset of symptoms are listed in Table 3. Among patients with neuroradiologic findings, the most common abnormality was PRES in 5 patients (4.6%). Other findings were ischemic stroke (3 patients, 2.8%), hemorrhagic stroke (1 patient, 0.9%), intra­cranial abscess (2 patients, 1.8%), and intracranial dissemination of sinusoidal fungal infection and related hemorrhagic infarct (1 patient, 0.9%). For patients who had PRES, CT, MRI, and diffusion-weighted MRI studies revealed vasogenic edema within the affected regions, with nonenhancing areas of low attenuation in CT and multiple areas of increased signal intensity in the subcortical white matter on T2-weighted images on MRI. For patients who had ischemic stroke, CT showed loss of gray-white matter differentiation and cortical hypodensity with associated parenchymal swelling with resultant gyral effacement. In patients with no evidence of stroke on CT, MRI and/or diffusion-weighted MRI revealed the infarction. In the patient with hemorrhagic stroke, CT easily disclosed the affected regions as hyperdense areas. In the patients who had intracranial abscesses, CT showed the hypodense cystic masses with vague or no prominent enhancement. In the patient with intracranial dissemination of sinusoidal fungal infection, MRI showed hyperintensities in the affected areas.

In the remaining 19 heart transplant recipients who underwent CT and/or MRI for neurologic complaints, no neuroradiologic findings related to neurologic symptoms were detected. The most common complaint was headache (n = 7; Table 2). In this patient group, time from transplant to onset of symptoms was 5 days to 6 years (mean of 14.5 mo). Some of these recipients showed chronic ischemic-hemorrhagic findings such as microangiopathic ischemic gliosis (n = 2), lacunar infarct (n = 2), encephalomalacia (n = 3), and chronic hemorrhagic area (n = 1) on CT and/or MRI. In addition, cerebral and/or cerebellar atrophy was observed at varying degrees in 7 of these patients (age range, 19-57 y, mean age of 40 y).

Discussion

Neurologic complications, which occur frequently in heart transplant recipients (23%-81%), markedly increase mortality and morbidity.3 Neurologic complications in such patients are influenced by their primary disease, prior cardiovascular and CNS status, the surgical procedure and postoperative course, and posttransplant medications. The most common complication in heart transplant recipients is ischemic stroke, which has been shown to occur in 3% to 10% of patients,^3,11 followed by drug toxicity and related PRES.⁷ Most strokes are due to ischemic infarctions; however, hemorrhagic strokes can also occur in 0.6% to 2.5% of heart transplant recipients.¹² Other early and late cerebrovascular complications include CNS infections, mass, and lympho­proliferative disorders.^1,4,5 In our series of heart transplant recipients with serious neurologic symptoms evaluated by neuroimaging, PRES was more commonly seen (4.6%), although ischemic stroke (2.8%) and hemorrhagic stroke (0.9%) also occurred. In addition, we observed occurrences of intracranial abscess (1.8%) and intracranial dissemination of sinusoidal fungal infection and related hemorrhagic infarct (0.9%).

Cardiovascular risk factors for ischemic stroke are present in many heart transplant patients, including hypertension, hyperlipidemia, atrial fibrillation, and diabetes mellitus.¹² Preoperative left ventricular assist device support, preoperative intraaortic balloon pump support, prolonged cardiopulmonary bypass time, postoperative hepatic failure, older age, the presence of extracranial carotid artery stenosis over 50%, pretransplant ventilator dependence, postoperative dialysis, infection requiring antibiotics before discharge, pacemaker implantation, and drug-treated hypertension during follow-up can all contribute to increased risk of cerebral infarction.^2,11,13 Furthermore, transplant-associated ischemic stroke is more common in patients transplanted for dilated cardiomyopathy, prior valvular disease, or congen­ital heart diseases.^3,13

In heart and liver allograft recipients, strokes occur earlier after transplant, whereas they tend to occur later after kidney transplant.¹⁴ According to the results of studies providing specific information about stroke pathogenesis after heart transplant, the ischemic stroke subtype distribution is different from the distribution observed in the general population. Specifically, large artery atherosclerosis (5%), small vessel disease (5%), and cardioembolism (15%) are seen less often, but unusual causes (35%) and un­determined causes (40%) occur more frequently.^1,11,15-17 In our series, 3 patients who developed ischemic stroke had dilated cardiomyopathy contributing to heart failure, with stroke occurring within 10 days of transplant in 2 patients and during the late period in 1 patient. Reasons contributing to ischemic stroke were embolism in 2 patients and undetermined cause in 1 patient (Figure 1).

Hemorrhagic stroke is usually caused by coagulation disorders, high pressure of the cardio­pulmonary bypass, and uncontrolled blood pressure.¹⁶ In heart transplant recipients, early perioperative hemorrhagic stroke may occur in the setting of pretransplant low cardiac output followed by posttransplant relative hyperperfusion associated with disordered cerebral autoregulatory pressor response.¹⁴ Lobar hemorrhagic stroke has been reported without coagulation disorders and uncontrolled blood pressure in up to 5% of patients, probably due to a mechanism of hyperperfusion.¹⁸ After heart transplant, hemorrhagic stroke is most commonly located in the deep (basal ganglia, thalamus, pons, and cerebellum) versus in the cerebral lobes.^1,3,11,15-18 In our series, 1 patient presented with multiple cerebral and cerebellar hematomas in both deep and lobar localizations and had subarachnoid hemorrhage due to throm­bocytopenia and probably due to mechanism of hyperperfusion (Figure 2).

Computed tomography and MRI are primary imaging methods used in patients who have suspected cerebrovascular diseases. The role of immediate CT in the management of acute cerebral infarction is crucial. Intracerebral hemorrhage can be rapidly diagnosed or excluded by CT. The CT findings in acute cerebral infarction evolve with time. Almost 60% of CT scans obtained within the first few hours after cerebral infarction are normal. Acute strokes are identified more often and localized more accurately with MRI than with CT scans. With the use of diffusion-weighted MRI, signal intensity changes can be detected within minutes of arterial occlusion. Acute infarcts have lower apparent diffusion coefficients than noninfarcted brain and may be a sensitive indicator of early cytotoxic brain edema.19 After the exclusion of intracerebral hemorrhage by CT in patients suspected of cerebrovascular disease, patients should immediately undergo MRI and/or diffusion-weighted MRI.

Posterior reversible leukoencephalopathy syn­drome is a clinical/radiologic syndrome characterized by alterations in mental status, personality changes, headaches, visual disturbances, and seizures. These symptoms can occur in the early postoperative period or later, emerging due to immunosuppressive treatment and accompanied by distinctive MRI findings.²⁰ Despite the proven efficacy of calcineurin inhibitors (cyclosporine and tacrolimus) to prevent acute rejection episodes and to enhance graft survival, recipients may develop PRES.^21,22 Posterior reversible leukoencephalopathy syndrome occurs more frequently in the presence of high blood levels of drugs; however, some patients have levels within the therapeutic range.²³ This syndrome may also be related to other changes induced by calcineurin inhibitors, including kidney insufficiency, hyper­tension, hypomagnesemia, hypocholesterolemia, and high doses of cortisone.⁴ Although it has been reported that 82% of cases occur within 90 days of transplant, presentation at 7.5 years posttransplant has also been reported.²⁴

Posterior reversible leukoencephalopathy syn­drome has been extensively described after bone marrow, liver, renal, and lung transplant but less in heart transplant recipients.^4,25 In PRES, the abnormalities are usually seen in a symmetric bilateral distribution involving mainly the parietal and occipital lobes, but involvement of temporal and frontal cortex and additional areas of the brain, including brain stem, cerebellum, and basal ganglia, has also been reported.^26-28 The pathophysiology of PRES and state of brain blood flow remain controversial. In early studies, vasoconstriction seen by catheter angiography prompted the authors to postulate that reduced brain perfusion led to the imaging features. In contrast, animal studies have suggested that experimentally induced hypertension above the autoregulatory limit led to hyperperfusion, break down of the blood-brain barrier, and hemispheric edema.^29,30 In PRES, hyperperfusion or hypoperfusion has been demonstrated in various diseases, including molar pregnancy, eclampsia, aneurysmal subarach­noid hemorrhage, after chemotherapy, and in autoimmune diseases, and with various imaging methods such as single-photon emission CT and magnetic resonance perfusion.^31-38 In addition, relative cerebral blood volume has been shown to be reduced moderately in areas of PRES (average of 65%) compared with normal uninvolved regions in 2 studies.^33,38 In their comparison of anterior versus posterior hemispheric flow, Brubaker and associates found that magnetic resonance perfusion demon­strated significant posterior brain hypoperfusion with increased mean transit time, reduced cerebral blood volume, and reduced cerebral blood flow.³⁷ After heart transplant, patients have shown residual frontal hypoperfusion on single-photon emission CT with 99m tchexamethyl-propylene-amineoxime,³⁹ and these cerebral anomalies may be because of long-standing cerebral hypoperfusion resulting from severe heart disease or microemboli caused by a cardiovascular bypass.¹² On the basis of these results, cerebral hyperperfusion followed by hypoperfusion resulting from severe heart disease may be a trigger of PRES in heart transplant recipients. Therefore, frontal involvement may be more common in heart transplant recipients. Indeed, in our series, 3 of 5 patients with PRES had frontal involvement (Figure 3).

In patients with PRES, radiologic findings may suggest reversible intracranial vasogenic edema. Brain CT results of patients with PRES are often normal. However, T2-weighted MRIs show high signals in affected areas. These findings are best demonstrated as hyperintense signals on fluid-attenuated inversion recovery sequence.²⁶ Increased diffusion on diffusion-weighted MRI may suggest vasogenic edema from endothelial damage rather than cytotoxic edema from regional ischemia.⁴⁰ These symptoms typically reverse promptly when the immunosuppressive treatment is changed or when drug doses are reduced.⁴ The clinical resolution of symptoms may then permit confirmation of PRES.⁴¹ Early recognition is essential, and delayed diagnosis may lead to status epilepticus, intracranial hemorrhage, ischemic infarction leading to neurologic damage, or death.⁴²

In heart transplant recipients who are receiving calcineurin inhibitors, central neurologic alterations should prompt radiologic imaging to investigate PRES. Magnetic resonance imaging should be the diagnostic procedure of choice. In our patients, associated seizures, hypertension, and renal impairment pointed toward anticalcineurin toxicity, although tacrolimus levels were within therapeutic ranges. The onset of these symptoms was within the first 3 months after transplant. Patients were treated symptomatically, resulting in clinical resolution of symptoms. Follow-up MRIs also revealed resolution of previous edema and cortical abnormalities.

More potent and effective immunosuppressive regimens have reduced the risk of graft rejection; however, these regimens have increased the susceptibility of transplant recipients to a variety of opportunistic CNS infections. These potentially life-threatening infections may be nonspecific and far from acute or obvious in transplant recipients.⁴³ Viral and fungal pathogens are more often implicated in opportunistic CNS infections in allograft recipients than bacteria and protozoa.²⁵ Central nervous system involvement is often metastatic from another site as part of systemic dissemination. Spread can also occur directly from sinuses.⁴³ The two most common pathogens are Cryptococcus and Aspergillus species. Munoz and associates reported that, among solid-organ transplant recipients, heart transplant recipients have the highest incidence of toxoplasmosis.⁴⁴ Orofacial aspergillosis is a rare clinical condition, which primarily affects, the paranasal sinuses, nasal cavity, mouth, facial skin, and orbit. The fungal lesions in the nasal, oral, and sinusoidal cavities may be the indirect result of thrombotic vascular infarction or dissem­ination to brain parenchyma.⁴⁵

Opportunistic CNS infections occur in about 5% to 10% of all renal transplant recipients.46 In heart transplant recipients, to our knowledge, the rates are unknown. Fungal CNS infections are fortunately becoming less common in transplant patients, but they still carry high mortality, and early and accurate diagnosis is of great importance.⁴⁷ Neuroimaging studies may show evidence of an abscess, encephalitis, or even brain infarction.⁹

The most common imaging characteristics of cerebral aspergillosis at CT or MRI are multiple lesions with infarction or hemorrhage in a random distribution due to the angioinvasive nature of the infection.⁴⁸

Abscesses may appear radiologically identical to other brain abscesses as classic ring-enhancing lesions with striking high signal intensity on diffusion-weighted imaging. However, contrast material enhancement may be vague or absent. A hypointense ring is often seen in the periphery of the lesions on T2-weighted MRIs. In cases where CNS aspergillosis is secondary to paranasal sinus disease, associated invasive rhinosinusitis, osteomyelitis, local dural enhancement, and subdural empyema may also be present.⁴⁸ Two patients in our heart transplant study group presented with abscesses within 3 months after heart transplant, which were diagnosed with CT. One patient had multiple hypodense cystic masses with no prominent peripheral enhancement, and the other patient had 1 lesion with vague peripheral enhancement after contrast medium administration. In one of these patients, Aspergillus fumigatus was isolated (Figure 4). Another patient was diagnosed with orofacial aspergillosis, which presented 7 years after heart transplant. The patient’s MRI showed extensive swelling and edema of right hemi-face, including orbita, infraorbital region, dorsum nasi, anterior of maxilla, parotid gland, infratemporal fossa, pterygoid muscles, and neck. T2-weighted images showed a hypointense nodular lesion in the right maxillary sinus suggesting fungal infection. Focal hyperintense signls consistent with focal cerebritis were present in the right temporal lobe, in the contiguity of cavernous sinus. Acute infarction findings were shown on the right cerebellum, vermis, and pons (Figure 5).

Of 31 study patients, 19 heart transplant recipients who underwent CT and/or MRI for neurologic complaints showed no radiopathologic finding related to symptoms. The most common complaint was headache in these patients. In their study, Donmez and colleagues reported similar findings for liver transplant recipients and suggested that headaches not accompanied by other complaints or objective signs could be evaluated initially by CT.⁴⁹ Other symptoms in our recipients were tremor, dizziness, sudden arm/leg weakness, and foot drop, which were probably related to side effects of drugs and transient ischemic attacks. Imaging studies in these patients showed chronic ischemic-hemorrhagic findings, including microangiopathic ischemic gliosis, lacunar infarct, encephalomalacia, and chronic hemorrhagic area. Also, cerebral-cerebellar atrophy was observed at varying degrees in patients at younger ages than in the normal population. These findings are related to advanced heart failure, decreased cerebral blood flow and hypoperfusion, underlying atherosclerosis, and antithrombotic drug use in these patients.

To investigate neurologic complications, CT is preferred for initial evaluation to rule out edema or hemorrhage. In the presence of serious neurologic symptoms that cannot be explained by CT findings, patients should have MRIs. However, agitated, lethargic, or potentially seizing patients might not remain still or safely undergo sedation for relatively lengthy routine MRI protocols. Therefore, some of our heart transplant recipients with neurologic complications were evaluated only by CT. A shorter MRI protocol may be devised in many instances, such as limiting the study to diffusion-weighted, gradient-echo, and T2-weighted images.⁴⁹

Conclusions

The most common neurologic complications in our heart transplant recipients were PRES and ischemic stroke. Other complications included hemorrhagic stroke, intracranial abscess, and intracranial dissemination of sinusoidal fungal infection. Neurologic complications are common in heart transplant recipients and should be identified promptly for early treatment. To investigate these complications, CT is preferred for initial evaluation to rule out edema or hemorrhage. However, when serious neurologic symptoms cannot be explained by CT findings, MRI should be indicated.

References:

1. van de Beek D, Kremers W, Daly RC, et al. Effect of neurologic complications on outcome after heart transplant. Arch Neurol. 2008;65(2):226-231.
   CrossRef - PubMed
   
2. Heroux A, Pamboukian SV. Neurologic aspects of heart transplantation. Handb Clin Neurol. 2014;121:1229-1236.
   CrossRef - PubMed
   
3. Perez-Miralles F, Sanchez-Manso JC, Almenar-Bonet L, Sevilla-Mantecon T, Martinez-Dolz L, Vilchez-Padilla JJ. Incidence of and risk factors for neurologic complications after heart transplantation. Transplant Proc. 2005;37(9):4067-4070.
   CrossRef - PubMed
   
4. Navarro V, Varnous S, Galanaud D, et al. Incidence and risk factors for seizures after heart transplantation. J Neurol. 2010;257(4):563-568.
   CrossRef - PubMed
   
5. Jaiswal A, Sabnani I, Baran DA, Zucker MJ. A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder. Am J Transplant. 2015;15(3):823-826.
   CrossRef - PubMed
   
6. Wright AJ, Fishman JA. Central nervous system syndromes in solid organ transplant recipients. Clin Infect Dis. 2014;59(7):1001-1011.
   CrossRef - PubMed
   
7. Senzolo M, Ferronato C, Burra P. Neurologic complications after solid organ transplantation. Transpl Int. 2009;22(3):269-278.
   CrossRef - PubMed
   
8. Server A, Bargallo N, Floisand Y, Sponheim J, Graus F, Hald JK. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation. Neuroradiology. 2017;59(2):105-126.
   CrossRef - PubMed
   
9. Zivkovic S. Neuroimaging and neurologic complications after organ transplantation. J Neuroimaging. 2007;17(2):110-123.
   CrossRef - PubMed
   
10. Guarino M, Benito-Leon J, Decruyenaere J, et al. EFNS guidelines on management of neurological problems in liver transplantation. Eur J Neurol. 2006;13(1):2-9.
    CrossRef - PubMed
    
11. Zierer A, Melby SJ, Voeller RK, et al. Significance of neurologic complications in the modern era of cardiac transplantation. Ann Thorac Surg. 2007;83(5):1684-1690.
    CrossRef - PubMed
    
12. Pizzi M, Ng L. Neurologic complications of solid organ transplantation. Neurol Clin. 2017;35(4):809-823.
    CrossRef - PubMed
    
13. Morgan CT, Manlhiot C, McCrindle BW, Dipchand AI. Outcome, incidence and risk factors for stroke after pediatric heart transplantation: An analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant. 2016;35(5):597-602.
    CrossRef - PubMed
    
14. Sila CA. Spectrum of neurologic events following cardiac transplantation. Stroke. 1989;20(11):1586-1589.
    CrossRef - PubMed
    
15. Adair JC, Call GK, O'Connell JB, Baringer JR. Cerebrovascular syndromes following cardiac transplantation. Neurology. 1992;42(4):819-823.
    CrossRef - PubMed
    
16. Belvis R, Marti-Fabregas J, Cocho D, et al. Cerebrovascular disease as a complication of cardiac transplantation. Cerebrovasc Dis. 2005;19(4):267-271.
    CrossRef - PubMed
    
17. Guillon B, Wiertlewski S, Trochu JN, et al. [Late cerebrovascular complications of cardiac transplantation]. Rev Neurol (Paris). 2000;156(3):264-269.
    PubMed
    
18. Acampa M, Lazzerini PE, Guideri F, Tassi R, Martini G. Ischemic stroke after heart transplantation. J Stroke. 2016;18(2):157-168.
    CrossRef - PubMed
    
19. Davis WL, Jacobs J. Cerebral vasculature: normal anatomy and pathology. In: Osborn AG, ed. Diagnostic Neuroradiology. St. Louis, MO: Mosby; 1994:154-385.
    
    
20. Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol. 2001;24(5):361-364.
    CrossRef - PubMed
    
21. Chow KM, Szeto CC. Posterior leukoencephalopathy with cyclosporine. Clin Nephrol. 2003;60(4):297-298; author reply 298.
    CrossRef - PubMed
    
22. Munoz R, Espinoza M, Espinoza O, Andrade A, Bravo E, Gonzalez F. Cyclosporine-associated leukoencephalopathy in organ transplant recipients: experience of three clinical cases. Transplant Proc. 2006;38(3):921-923.
    CrossRef - PubMed
    
23. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression. Neurology. 1995;45(11):1962-1964.
    CrossRef - PubMed
    
24. Tsagalou EP, Anastasiou-Nana MI, Margari ZJ, Vassilopoulos D. Possible everolimus-induced, severe, reversible encephalopathy after cardiac transplantation. J Heart Lung Transplant. 2007;26(6):661-664.
    CrossRef - PubMed
    
25. Pless M, Zivkovic SA. Neurologic complications of transplantation. Neurologist. 2002;8(2):107-120.
    CrossRef - PubMed
    
26. Lamy C, Oppenheim C, Meder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging. 2004;14(2):89-96.
    CrossRef - PubMed
    
27. Arnoldus EP, Van Laar T. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(26):1745; author reply 1746.
    PubMed
    
28. Gijtenbeek JM, van den Bent MJ, Vecht CJ. Cyclosporine neurotoxicity: a review. J Neurol. 1999;246(5):339-346.
    CrossRef - PubMed
    
29. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol. 2008;29(6):1036-1042.
    CrossRef - PubMed
    
30. Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol. 2008;29(6):1043-1049.
    CrossRef - PubMed
    
31. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol. 1995;165(3):627-631.
    CrossRef - PubMed
    
32. Sanchez-Carpintero R, Narbona J, Lopez de Mesa R, Arbizu J, Sierrasesumaga L. Transient posterior encephalopathy induced by chemotherapy in children. Pediatr Neurol. 2001;24(2):145-148.
    CrossRef - PubMed
    
33. Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2008;29(3):447-455.
    CrossRef - PubMed
    
34. Apollon KM, Robinson JN, Schwartz RB, Norwitz ER. Cortical blindness in severe preeclampsia: computed tomography, magnetic resonance imaging, and single-photon-emission computed tomography findings. Obstet Gynecol. 2000;95(6 Pt 2):1017-1019.
    CrossRef - PubMed
    
35. Lewis DH, Hsu S, Eskridge J, et al. Brain SPECT and transcranial Doppler ultrasound in vasospasm-induced delayed cerebral ischemia after subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 1992;2(1):12-21.
    CrossRef - PubMed
    
36. Naidu K, Moodley J, Corr P, Hoffmann M. Single photon emission and cerebral computerised tomographic scan and transcranial Doppler sonographic findings in eclampsia. Br J Obstet Gynaecol. 1997;104(10):1165-1172.
    CrossRef - PubMed
    
37. Brubaker LM, Smith JK, Lee YZ, Lin W, Castillo M. Hemodynamic and permeability changes in posterior reversible encephalopathy syndrome measured by dynamic susceptibility perfusion-weighted MR imaging. AJNR Am J Neuroradiol. 2005;26(4):825-830.
    PubMed
    
38. Engelter ST, Petrella JR, Alberts MJ, Provenzale JM. Assessment of cerebral microcirculation in a patient with hypertensive encephalopathy using MR perfusion imaging. AJR Am J Roentgenol. 1999;173(6):1491-1493.
    CrossRef - PubMed
    
39. Burra P, Senzolo M, Pizzolato G, et al. Frontal cerebral blood flow is impaired in patients with heart transplantation. Transpl Int. 2002;15(9-10):459-462.
    CrossRef - PubMed
    
40. Coley SC, Porter DA, Calamante F, Chong WK, Connelly A. Quantitative MR diffusion mapping and cyclosporine-induced neurotoxicity. AJNR Am J Neuroradiol. 1999;20(8):1507-1510.
    PubMed
    
41. Singh N, Bonham A, Fukui M. Immunosuppressive-associated leukoencephalopathy in organ transplant recipients. Transplantation. 2000;69(4):467-472.
    CrossRef - PubMed
    
42. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Intern Med J. 2005;35(2):83-90.
    CrossRef - PubMed
    
43. Dhar R, Human T. Central nervous system complications after transplantation. Neurol Clin. 2011;29(4):943-972.
    CrossRef - PubMed
    
44. Munoz P, Valerio M, Palomo J, et al. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore). 2010;89(3):166-175.
    CrossRef - PubMed
    
45. Dreizen S, Bodey GP, McCredie KB, Keating MJ. Orofacial aspergillosis in acute leukemia. Oral Surg Oral Med Oral Pathol. 1985;59(5):499-504.
    CrossRef - PubMed
    
46. Acar T, Arshad M. Nocardia asteroides cerebral abscess in a renal transplant recipient: short report. Acta Chir Belg. 2002;102(6):470-471.
    CrossRef - PubMed
    
47. Singh N, Avery RK, Munoz P, et al. Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clin Infect Dis. 2003;36(1):46-52.
    CrossRef - PubMed
    
48. DeLone DR, Goldstein RA, Petermann G, et al. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol. 1999;20(9):1597-1604.
    PubMed
    
49. Donmez FY, Guvenc Z, Emiroglu FK, Coskun M, Haberal M. Evaluation of neurological complications in pediatric liver transplant recipients: MRI versus CT. J Child Neurol. 2009;24(6):656-663.
    CrossRef - PubMed