NDT Advance Access originally published online on May 15, 2006
Nephrology Dialysis Transplantation 2006 21(7):2017-2019; doi:10.1093/ndt/gfl239
© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Teaching Point
A patient recently transplanted with a living donor kidney develops severe neurological symptoms
Susanne Heiss1,
Wolfgang Krampla2 and
Renate Klauser-Braun1
1 3rd Medical Department and 2 Radiology Department, Donauspital, Vienna, Austria
Correspondence and offprint requests to: Susanne Heiss, 3rd Medical Department, Donauspital, Langobardenstrasse 122, A-1220 Vienna, Austria. Email: susanne.heiss{at}wienkav.at
Keywords: ciclosporin A; kidney transplant; malignant hypertension; side effects
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Case
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One week after receiving a kidney transplant donated by his
father, a 20-year-old patient was transferred to our department.
The history of his kidney problems started when he was 1 year
old. He had obstructive nephropathy requiring repeat urological
operations and resulting in end-stage renal failure necessitating
chronic haemodialysis from the age of 8 until this recent transplantation.
His post-transplantation immunosuppressive regimen consisted
of ciclosporin, mycofenolate mofetil and prednisone. A few days
after his transfer to our department, he developed a biopsy-proven
borderline transplant rejection, which was treated with high
doses of cortisone. His repeated complaints of headaches were
attributed to the cortisone, and they resolved without any treatment.
A few days later, he developed blurred vision in the right eye,
and that was followed by a generalized seizure. On the very
same day—the 15th day after his kidney transplantation—he
had to be transferred to the intensive care unit for a status
epilepticus.
His blood pressure was normal—the highest ever being 150/80 mmHg. His blood tests on the day of the onset of neurological symptoms showed the following: BUN 23 mg/dl, creatinine 1.0 mg/dl, Na 134 mmol/l, K 3.8 mmol/l, Ca 2.1 mmol/l, erythrocytes 3.7 x 106/l, haematocrit 37%, haemoglobin 12.5 g/l, leucocytes 8200/l, thrombocytes 246 000/l, albumin 33 g/l, CRP 3 mg/l. Apart from the time of borderline rejection, when his creatinine rose to a maximum of 1.6 mg/dl, his blood tests were normal throughout his stay in the department. His ciclosporin trough levels had a mean value of around 250 ng/ml.
Computed tomography (CT) showed hypodense areas mainly in the posterior white matter of his brain. Our radiologist suspected a posterior reversible encephalopathy syndrome (PRES). Magnetic resonance tomography (MRT) confirmed the diagnosis of PRES by showing the characteristic hyperintense parieto-occipital white matter lesions in the T2-weighted images (Figures 1 and 2). There was no involvement of the grey matter.
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Fig. 1. The MRI of the patient's brain 3 days after the onset of symptoms shows the characteristic diffuse hyperintensities.
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Ciclosporin was discontinued immediately and replaced with rapamycin.
Our patient recovered within days, showing no residual symptoms.
A follow-up MRT was normal (
Figure 3): all lesions had resolved.
He has since been asymptomatic, with a serum creatinine of 0.9
mg/dl, and on an immunosuppressive regimen consisting of rapamycin,
mycofenolate mofetil and low dose prednisone.
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Discussion
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The posterior reversible encephalopathy syndrome was first described
by Hinchey
et al. [
1]. It was then referred to as the leukencephalopathy
syndrome. Hinchey reported on 15 patients diagnosed with this
syndrome with varying triggers. The earliest description of
epileptic fits in transplant patients is by Adams
et al. [
2]
in 1987. In their article, the authors claim the evidence implicating
ciclosporin in the development of fits to be strong. The syndrome
was later renamed as to posterior reversible encephalopathy
syndrome, because of its greater accuracy.
PRES can be triggered by interferon-
, IV immunoglobulin, erythropoetin, cisplatin and cytarabine, or it can be associated with diseases like lupus erythematosus, panarteritis nodosa, AIDS or thrombotic-thrombocytopenic purpura. However, most cases of PRES are described in association with eclampsia, malignant hypertension and immunosuppressive therapy [3]. The most frequent triggers among immunosuppressants are calcineurin inhibitors, among those ciclosporin being more prone to cause PRES than tacrolimus [4]. The symptoms of PRES typically occur around day 14 of calcineurin inhibitor therapy. Though the mechanism of brain injury is not fully known, the posterior localization of the damage is thought to be due to the lack of sympathetic fibres in the posterior cerebral arteries; the hyperperfusion and oedema are suggested to be responses to a hypertensive or toxic damage to the wall of the vessels [3].
The common clinical features of PRES are headache and seizures [3]. The onset is acute, with rapid progression to multiple seizures, usually of the generalized tonic–clonic type. Other neurological symptoms, like confusional states, vomiting, visual disturbances—such as haemianopia, or cortical blindness, and occasionally focal neurological deficits may follow. Occasionally, coma may also develop [3].
The differential diagnosis of PRES includes various acute neurological conditions, such as stroke, cerebral venous thrombosis, encephalitis and demyelinating disorders. As mentioned earlier, the diagnosis is made mainly by radiologists [5]. CT scans of the brain show bilateral and mostly symmetrical hypodense areas in the parietal and occipital white matter; the involvement of the grey matter, however, is also possible. The lesions are best visualized by magnetic resonance imaging (MRI). T2-weighted MRIs show characteristically diffuse hyperintensities selectively involving the parieto-occipital white matter. The lesions are even better demonstrated by fluid attenuated inversion recovery imaging (FLAIR, another special MRI technique) where the cerebrospinal fluid signal is nulled to emphasize the oedematous lesions [6]. MRI also rules out cerebral venous thrombosis, demyelinating diseases and ischaemic stroke, the latter by diffusion-weighted imaging, another MRI technique [7]. Diagnosing viral encephalitis is difficult, and for this a lumbar puncture may be needed [3].
With PRES, it is of paramount importance to identify and treat the underlying cause rapidly, e.g. in our case, by discontinuing calcineurin inhibitor therapy. Furthermore, it is extremely important to recognize a PRES, because an adequate therapy for PRES is different from that therapy of other neurological conditions. While moderate hypertension would not be treated in an ischaemic stroke, for example, it must be treated vigorously in PRES to reverse the pathological process before it causes permanent brain injury [3]. With rapid elimination of the cause, most PRES are fully reversible within days. There are, however, cases reported in the literature where symptoms did not fully resolve, especially when the lesions were not restricted to the white matter or when there was a delay in the administration of the correct therapy [8].
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Teaching points
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- If a patient develops severe neurological symptoms about 2 weeks after the inititation of calcineurin inhibitor therapy, consider the possibility of the patient having a posterior reversible encephalopathy syndrome. PRES can also occur with hypertension, eclampsia and with a variety of drugs and diseases.
- The onset of PRES is acute, and with heavy neurological symptoms, often including headache and seizures.
- PRES is diagnosed by the radiologist, based on its typical patterns in the CT scan, or more reliably, based on an MRI of the brain. Differentiation from other cerebral injuries is made by special MRI techniques.
- PRES is generally reversible, especially when treated rapidly. The treatment is simply the withdrawal of the calcineurin inhibitor therapy, or, if PRES is due to hypertension, normalization of blood pressure.
Conflict of interest statement. None declared.
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References
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- Hinchey J, Chaves C, Appignani B et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500[Abstract/Free Full Text]
- Adams DH, Ponsford S, Gunson B et al. Neurological complications following liver transplantation. Lancet 1987; 1: 949–951[Web of Science][Medline]
- Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med J 2001; 77: 24–28[Abstract/Free Full Text]
- Cosottini M, Lazzarotti G, Ceravolo R, Michelassi MC, Canapicchi R, Murri L. Cyclosporine-related posterior reversible encephalopathy syndrome (PRES) in non-transplant patient: a case report and literature review. Eur J Neurol 2003; 10: 461–462[Medline]
- Furukawa M, Terae S, Chu BC, Kaneko K, Kamada H, Miyasaka K. MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging. Neuroradiology 2001; 43: 615–621[CrossRef][Web of Science][Medline]
- Casey SO, Sampaio RC, Michel E, Truwit CL. Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions. Am J Neuroradiol 2000; 21: 1199–1206[Abstract/Free Full Text]
- Chou MC, Lai PH, Yeh LR et al. Posterior reversible encephalopathy syndrome: magnetic resonance imaging and diffusion-weighted imaging in 12 cases. Kaohsiung J Med Sci 2004; 20: 381–388[Medline]
- Antunes NL, Small TN, George D, Boulad F, Lis E. Posterior leukoencephalopathy syndrome may not be reversible. Pediatr Neurol 1999; 20: 241–243[CrossRef][Web of Science][Medline]
Received for publication: 28. 2.06
Accepted in revised form: 27. 3.06
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