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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 3  |  Page : 439-442
Cyclosporin-A induced Posterior Reversible Encephalopathy Syndrome


1 Division of Pediatric Nephrology, Surgical Kidney Hospital, Ibn-Alnafis Medical Complex, Damascus, Syria
2 Medical Department, Sweidaah Hospital, Sweidaah, Syria

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   Abstract 

Posterior reversible encephalopathy syndrome (PRES) is a recently proposed clinico­neuroradiological entity observed in a variety of clinical settings such as cyclosporin A (CsA) neurotoxicity. We report a 3.5-year-old Syrian boy in whom steroid-resistant focal segmental glomerulosclerosis (FSGS) was recently diagnosed. The patient remitted his nephrotic syndrome after 10 days of CsA administration. However, he shortly developed altered mental status, visual impairment, focal neurological deficits and seizures. We discontinued CsA that resulted in complete reversal of the patient's encephalopathical condition over a period of 4 months. We conclude that PRES should be suspected in immunosuppresed patients with kidney disease if they have a sudden episode of neurological symptoms.

Keywords: Nephrotic syndrome, Cyclosporin, Neurotoxicity, Hypertension, Posterior Reversible Encephalopathy Syndrome

How to cite this article:
Saeed B, Abou-Zor N, Amer Z, Kanani I, Hilal M. Cyclosporin-A induced Posterior Reversible Encephalopathy Syndrome. Saudi J Kidney Dis Transpl 2008;19:439-42

How to cite this URL:
Saeed B, Abou-Zor N, Amer Z, Kanani I, Hilal M. Cyclosporin-A induced Posterior Reversible Encephalopathy Syndrome. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Aug 17];19:439-42. Available from: http://www.sjkdt.org/text.asp?2008/19/3/439/40507

   Introduction Top


Posterior reversible encephalopathy syn­drome (PRES) is a distinctive clinicoradio­logical entity observed in a variety of clini­cal settings and is clinically characterized by altered mental status, visual impairment, focal neurological deficits and seizures. [1] A grea­ter prevalence of this syndrome has been suggested in kidney transplant recipients and patients with kidney disease. Although usua­lly considered benign and reversible, charac­teristics of PRES in pediatric patients remain obscure and the exact pathophysiology has not yet been defined. [1]

The most common causes of PRES are hypertensive encephalopathy, eclampsia, cy­closporine (CsA) neurotoxicity, and the ure­mic encephalopathy. On magnetic resonance imaging (MRI) studies, edema has been repor­ted in a relatively symmetrical pattern, typi­cally in the subcortical white matter. [2] The diffusion-weighted MRI and proton MR spectroscopy findings in the case of cyclos­porin induced encepahalopathy have illus­trated the presence of white-matter lesions with reversible restricted diffusion, which supported the hypothesis of reversible vaso­spasm induced by CsA. [3]


   Case Report Top


A 3.5-year-old Syrian boy was referred to our hospital due to a steroid-resistant neph­rotic syndrome; he did not remit after 4 weeks treatment with prednisolone. The chief complaint was increasing generalized edema with decreasing urine output during the last few days prior to admission. The clinical examination revealed severe anasacra with 130/80 mmHg blood pressure.

Laboratory investigations revealed severe hypoalbuminemia, hypercholesterolemia, hy­pertriglyceridemia, 1 gram per 24-hour pro­teinuria (nephrotic range for the patient's weight), and within normal limits C3, C4, Anti DNA, ANA, and liver enzymes.

The initial therapeutic approach included albumin infusion and i.v. furosemide to in­duce diuresis, methylprednisolone bolus doses for 3 consecutive days to induce remission, and conservative management. The patient continued to be severely edematous with increased proteinuria after the third bolus dose of methylprednisolone. Hence, a kidney biopsy was performed and revealed 21 glo­meruli; 1 of them demonstrated FSGS, while The others disclosed normal size and cellu­larity. The interstitium, tubules, and vessels were normal, [Figure - 1].

Accordingly, the clinico-pathological diag­nosis was mostly compatible with FSGS, and the patient was started on CsA, combined with prednisolone, albumin infusions, loop diuretic, and other conservative management. Ten days later, the patient attained complete remission of his nephrotic syndrome and he was completely asymptomatic for 2 days. Then, suddenly he started to have brief attacks of abnormal eye movements, altered cons­ciousness followed by a generalized sei­zures that responded to diazepam injection. The patient was afebrile, moderately hyper­tensive (130/90-mmHg), and his fundus examination revealed mild edema. Blood investigations did not detect any metabolic abnormalities. A lumber puncture was per­formed and disclosed normal CSF. We trans­ferred the patient to a pediatric ICU, where he developed recurrent other attacks of con­vulsions necessitating intravenous phenytoin administration, which succeeded in contro­lling them. A brain magnetic resonance image revealed bilateral high signal intensities on T2-weighted images in the subcortical and deep white matter areas of the temporal, frontal, parietal, and occipital lobes, [Figure - 2].

An electro-encephalogram demonstrated non-specific diffuse findings consistent with encephalopathy. We considered CsA as a possible cause for the convulsive encepha­lopathy, hence, we discontinued it. Shortly thereafter, the patient relapsed his nephrotic syndrome, which necessitated resuming in­termittent albumin infusion along with diu­retics. He remained deeply comatose for 15 days before he started to recover and im­prove very slowly his Glasgow score which took almost 2 months before he became fully conscious.

However, he experienced some degree of vision impairment and mild to moderate muscle weakness of his lower limbs, which was mostly attributable to the prolonged course of his sickness. The antiepileptic drugs discontinued, and 4 months later, he was stable with appropriate psychomotor development for his age, but still with mild vision impairment as a sequela.


   Discussion Top


Seizures, altered conscious level, and im­paired vision were the major clinical mani­festations in our case. This clinical presen­tation along with the neuro-imaging features that occurred in the context of CsA use in a hypertensive child was compatible with the diagnosis of PRES. Later on, this diagnosis was confirmed with the patient's favorable response to the discontinuation of CsA and ultimately his almost full reversal of his enecephalopathy.

Common adverse reactions of immuno­suppressive treatment (e.g. CsA) are infec­tions, hematological and liver function abnor­malities, and neurological complications. [4]

Hypertensive encephalopathy, [5],[6],[7],[8] renal failure, [5] immunosuppressive therapy [5],[9],[10] and eclamp­sia, [11],[12] have been reported to be major causes of PRES. This syndrome is essentially hy­pertensive encephalopathy with decreased threshold in immunosuppressed patients. Our patient had more than one contributory factor as he was hypertensive and received CsA.

The white matter lesions in our patient were symmetrical and diffuse rather than confined to the posterior parieto-occipital lobes as described in literature. [2],[13] However, the almost complete recovery of our patient with the exception of his mild vision im­pairment supports the hypothesis of rever­sible vasospasm induced by cyclosporine. [3] Continuous focal rhythmic activities in the EEG during the acute period that norma­lized after the clinical manifestations had disappeared have been reported. [14] The EEG findings in our case were not useful for the diagnosis of PRES, however, we strongly believe that EEG might be useful not only for the diagnosis of PRES but also for the follow-up. [14]

We conclude that PRES should be sus­pected in immunosuppressed patients with kidney disease if they have a sudden epi­sode of neurological symptoms, even if imaging findings are not restricted to the subcortical white matter of the occipital lobe.

 
   References Top

1.Ishikura K, Ikeda M, Hamasaki Y, et al. Posterior reversible encephalopathy syndrome in children: Its high prevalence and more extensive imaging findings. Am J Kidney Dis 2006;48(2):231-8  Back to cited text no. 1    
2.Gokce M, Dogan E, Nacitarhan S, Demirpolat G. Posterior reversible encephalopathy syndrome caused by hypertensive encephalopathy and acute uremia. Neurocrit Care 2006;4(2):133-6.  Back to cited text no. 2    
3.Aydin K, Donmez F, Tuzun U, et al. Diffusion MR findings in cyclosporin: A induced ence­ phalopathy. Neuroradiology 2004;46(10):822-4.  Back to cited text no. 3    
4.Shin KC, Choi HJ, Bae YD, Lee JC, Lee EB, Song YW. Reversible posterior leukoencephalo­pathy syndrome in systemic lupus erythema­tosus with thrombocytopenia treated with cyclos­porine. J Clin Rheumatol 2005;11(3):127-8.  Back to cited text no. 4    
5.Hinchey J, Chaves C, Appignani B, et al. Reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334(8):494-500.  Back to cited text no. 5    
6.Haisser RA, Lacey DM, Knight MR. Hypertensive encephalopathy: Magnetic reso­nance imaging demonstration of reversible cortical and white matter lesions. Arch Neurol 1988;45(10):1078-83.  Back to cited text no. 6    
7.Schwartz RB, Jones KM, Kalina P, et al. Hypertensive encephalopathy: Findings on CT, MR imaging and SPECT imaging in 14 cases. AJR Am J Roentgenol 1992;159(2):379-83.  Back to cited text no. 7    
8.Sheth TN, Ichise M, Kucharczyk W. Brain perfusion imaging in asymptomatic patients receiving cyclosporine. AJNR Am J Neuroradiol 1999;20(5):853-6.  Back to cited text no. 8    
9.Schwarz 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):627-9.  Back to cited text no. 9    
10.Shutter LA, Green JP, Newman NJ, Hooks MA, Gordon RD. Cortical blindness and white matter lesions in a patient receiving FK506 after liver transplantation. Neurology 1993;43(11):2417-8.  Back to cited text no. 10    
11.Digre KB, Varner MW, Osborn AG, Crawford S. Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia. Arch Neurol 1993;50(4):399-406.  Back to cited text no. 11    
12.Schwartz RB, Feske SK, Polak JF, et al. Preeclampsia-eclampsia: Clinical and neuro­radiographic correlates and insights into the pathogenesis of hypertensive encephalopathy. Radiology 2000;217(2):371-6.  Back to cited text no. 12    
13.Javed MA, Sial MS, Lingawi S, Alfi A, Lubbad E. Etiology of posterior reversible Encephalopathy syndrome (PRES). Pak J Med Sci 2005;21(2):149-54.  Back to cited text no. 13    
14.Natsume J, Sofue A, Yamada A, Kato K. Electroencephalographic (EEG) findings in posterior reversible encephalopathy associated with immunosuppressants. J Child Neurol 2006;21(7):620-3.  Back to cited text no. 14    

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Correspondence Address:
Bassam Saeed
Pediatric Nephrologist, Division of Pediatric Nephrology, Surgical Kidney Hospital, P.O. Box 8292 Damascus
Syria
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PMID: 18445907

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    Abstract
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