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Table of Contents
Year : 2022  |  Volume : 16  |  Issue : 3  |  Page : 325-327

Persistent headache in a young kidney transplant recipient caused by tacrolimus associated pseudotumor cerebri - A case report

1 Department of Nephrology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of Neurology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Submission28-Jun-2021
Date of Acceptance03-Nov-2021
Date of Web Publication30-Sep-2022

Correspondence Address:
Dr. Prit Pal Singh
Department of Nephrology, Indira Gandhi Institute of Medical Sciences, Patna - 800 014, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_66_21

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Pseudotumor cerebri (PC) is characterized by chronic elevation of intracranial pressure with normal cerebrospinal fluid (CSF) examination and normal neuro-imaging. We report a case of a 22-year-old female with renal allograft and for the past 4 years on immunosuppressant including prednisolone, tacrolimus, and mycophenolate mofetil. The patient presented with persistent headache for 2 months along with nausea and vomiting. Fundoscopic examination revealed bilateral papilledema. Magnetic resonance imaging-brain with venogram was normal and cytochemical examination of CSF was also normal. Ocular coherence tomography revealed increased retinal nerve fiber layer thickness. A diagnosis of PC was made based on an elevated CSF pressure (35 cm H20). We reduced the dose of tacrolimus and added acetazolamide but the dose of prednisolone and mycophenolate mofetil was not modified. There was the gradual improvement of symptoms. On follow-up visits, papilledema disappeared and the patient is now asymptomatic with normal allograft function.

Keywords: Headache, intracranial hypertension, kidney transplant, pseudotumor cerebri, tacrolimus

How to cite this article:
Singh PP, Krishna A, Mazumdar P, Ranjan A. Persistent headache in a young kidney transplant recipient caused by tacrolimus associated pseudotumor cerebri - A case report. Indian J Transplant 2022;16:325-7

How to cite this URL:
Singh PP, Krishna A, Mazumdar P, Ranjan A. Persistent headache in a young kidney transplant recipient caused by tacrolimus associated pseudotumor cerebri - A case report. Indian J Transplant [serial online] 2022 [cited 2022 Nov 27];16:325-7. Available from: https://www.ijtonline.in/text.asp?2022/16/3/325/357612

  Introduction Top

Pseudotumor cerebri (PC) is a relatively rare but important treatable cause of headache in kidney transplant recipients. PC is characterized by chronic elevation of intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) examination and normal neuroimaging.[1] PC has mostly been reported after bone marrow transplantation[2] and rarely in kidney transplant recipients.[3],[4] Long-term use of steroids and cyclosporine are known to be associated with elevated ICP.[1],[2],[3],[4],[5] Most cases of PC in kidney transplant recipients have been reported in the pediatric population associated with Cyclosporine A (CsA).[1],[3],[4],[5] Association with tacrolimus is not known except for one report by Chamberlain et al.[6] Here, we describe a case of PC associated with tacrolimus in a young female kidney transplant recipient.

  Case Report Top

A 22-year-old young female, who received a live kidney from her mother in June 2015 was on prednisolone (5 mg/day), tacrolimus (2.5 mg/day), and mycophenolate mofetil (1.5 g/day). Fifty two months after transplantation, she presented in October 2019 with persistent headache for the last 1–2 months which increased over the next 7–10 days along with nausea and intermittent vomiting. There was no history of any significant medical illness posttransplant. Laboratory findings revealed serum creatinine- 1.7 mg/dL, blood urea nitrogen-37 mg/dL, tacrolimus level-5.5 ng/mL, Hb 12.8 g/L and normal serum electrolytes.

On examination, blood pressure was 134/82 mmHg, heart rate 74/min, and respiratory rate 14/min and was dehydrated. Her body mass index was 23.1 Kg/m2 (weight-52 kg, height- 157 cm). Neurological examination revealed no abnormality including the normal movement of extrinsic eye musculature. Other systemic examinations were nonrevealing.

On ophthalmic examination, visual acuity in the right and left eyes were 6/6 and 6/12 respectively and pupillary reflexes were normal. Fundoscopy revealed blurring of both optic disc margins and obscuration of vessels at disc margin suggestive of bilateral papilledema [Figure 1]. Optical coherence tomography showed increased retinal nerve fiber layer thickness in the left eye [Figure 2].
Figure 1: Fundoscopy showing blurring of optic disc margin and obscuration of vessels as they leave the disc suggestive of B/L papilledema

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Figure 2: Ocular coherence tomography showing increased retinal nerve fiber layer thickness suggestive of papilledema

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Magnetic resonance imaging of the brain with venography was normal. CSF examination revealed-four leukocytes (100% mononuclear cells), glucose 69 mg/dL, protein 37 mg/dL with increase in opening CSF pressure (35 cm H20). CSF evaluation including Gene expert, adenosine deaminase, and Ziehl–Neelsen staining for tuberculosis, gram stain and culture for bacteria, and India ink stain and cryptococcal antigen test were all negative.

Dehydration and prerenal acute graft dysfunction responded to intravenous hydration with normal saline (serum creatinine 1.3 mg/dl).

With persistent headache, papilledema, significantly raised ICP, normal CSF study and normal brain imaging, diagnosis of PC was made. In view of no refractory error, CNS, or orbital structural defect, we suspected tacrolimus (Tacrolimus C0 level = 5.9 ng/ml) as the etiology of this secondary elevation in the ICP as steroid use in such a small dose was unlikely to cause raised ICP. Tacrolimus dose was reduced gradually to keep tacrolimus level around 3–4 ng/ml, but the dose of mycophenolate mofetil and steroid remained the same and acetazolamide was administered.

The patient's symptoms gradually subsided, and she was discharged from the hospital after 2 weeks. Acetazolamide was stopped after 2 months. On the last follow-up done 18 months from presentation, symptoms did not recur and the patient is having normal graft function.

  Discussion Top

PC may be primary (idiopathic intracranial hypertension, [IIH]) or arise from a secondary cause. IIH is a diagnosis of exclusion. A drug-induced rise in the ICP is considered a secondary form of PC.[7]

PC has been associated, with a number of drugs like Tetracycline and related compounds, Vitamin A, Amiodarone, Growth hormone, Levothyroxine (children), Lithium carbonate, Nalidixic acid, Levonorgestrel, and Sulfa antibiotics.[7] Majority of PC cases in kidney transplant recipients have been reported in the pediatric population and were associated with Cyclosporine.[1],[3],[4],[5] PC is associated with chronic high dose steroid therapy[8] or abrupt steroid withdrawal after a prolonged intake.[9]

Neurological side-effects secondary to the use of calcineurin inhibitors (CNIs) may occur in 0.5% to 35% of patients and range from headaches, paresthesia, tremors to seizures, however, CsA has also been associated with elevation of ICP.[1],[3],[4],[5] Avery et al.[2] reported eight cases of optic disc edema in patients taking CsA after allogeneic bone marrow transplant which resolved after discontinuing or decreasing the dose of CsA.

Most cases of PC in renal allograft recipients have been reported in the pediatric population and less commonly in adults [Table 1]. On review of literature; we found only one case reported with Tacrolimus by Chamberlain et al.[6]
Table 1: Case reports of idiopathic intracranial hypertension associated with cyclosporine and tacrolimus

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Tacrolimus causes microangiopathy of the optic nerve head and this microangiopathy leads to the development of focal atrophy and subsequent development of papilledema.[10],[11] The relationship with serum CNI level is inconsistent and papilledema is thought to be due to an idiosyncratic response. In our patient, the blood level of tacrolimus was within the normal limits (5–6 ng/ml), so PC was most likely due to idiosyncratic response.

If untreated, papilledema can result in progressive and irreversible vision loss with optic atrophy.[12],[13],[14] The mainstay of medical treatment is avoiding or decreasing the dose of the offending drug, addition of the carbonic anhydrase inhibitors,[13] combined with weight reduction for those considered clinically overweight. When medical management fails to produce the desired effect, surgical interventions such as CSF shunting, optic nerve sheath fenestration, and transverse venous sinus stenting are necessary to preserve visual function.[14]

In renal transplantation patients, decreasing immunosuppressant risk graft rejection, we continued low dose steroid and Mycophenolate mofetil as before but reduced the dose of tacrolimus and added acetazolamide. Patient's symptoms improved gradually and papilledema finally disappeared. On follow-up, headache and papilledema disappeared, and the patient was asymptomatic with normal allograft function, thus emphasizing the importance of early diagnosis and management.

  Conclusion Top

In renal transplantation patients on immunosuppressant with persistent headache, detailed evaluation must be done to rule out central nervous system involvement. When the initial evaluation is unrevealing, rare causes like PC should be considered. In this case report, we have shown that tacrolimus can rarely be associated with PC in kidney transplant recipients. Complete resolution of symptoms may be achieved with prompt intervention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Francis PJ, Haywood S, Rigden S, Calver DM, Clark G. Benign intracranial hypertension in children following renal transplantation. Pediatr Nephrol 2003;18:1265-9.  Back to cited text no. 1
Avery R, Jabs DA, Wingard JR, Vogelsang G, Saral R, Santos G. Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity. Ophthalmology 1991;98:1294-301.  Back to cited text no. 2
Katz B. Disk edema subsequent to renal transplantation. Surv Ophthalmol 1997;41:315-20.  Back to cited text no. 3
Lee SJ, Jung YS, Rim H, Yoo BG. Successful switch to tacrolimus in a patient with pseudotumor cerebri following cyclosporine a treatment in renal transplantation. Dial Transplant 2009;38:374-6.  Back to cited text no. 4
Costa KM, Almeida JB, Félix RH, Silva Júnior MF. Pseudotumor cerebri associated with cyclosporin use following renal transplantation. J Bras Nefrol 2010;32:136-9.  Back to cited text no. 5
Chamberlain CE, Fitzgibbon E, Wassermann EM, Butman JA, Kettl D, Hale D, et al. Idiopathic intracranial hypertension following kidney transplantation: A case report and review of the literature. Pediatr Transplant 2005;9:545-50.  Back to cited text no. 6
Friedman DI. The pseudotumor cerebri syndrome. Neurol Clin 2014;32:363-96.  Back to cited text no. 7
Levine A, Watemberg N, Hager H, Bujanover Y, Ballin A, Lerman-Sagie T. Benign intracranial hypertension associated with budesonide treatment in children with Crohn's disease. J Child Neurol 2001;16:458-61.  Back to cited text no. 8
Liu GT, Kay MD, Bienfang DC, Schatz NJ. Pseudotumor cerebri associated with corticosteroid withdrawal in inflammatory bowel disease. Am J Ophthalmol 1994;117:352-7.  Back to cited text no. 9
Bernauer W, Gratwohl A, Keller A, Daicker B. Microvasculopathy in the ocular fundus after bone marrow transplantation. Ann Intern Med 1991;115:925-30.  Back to cited text no. 10
Walter SH, Bertz H, Gerling J. Bilateral optic neuropathy after bone marrow transplantation and cyclosporin A therapy. Graefes Arch Clin Exp Ophthalmol 2000;238:472-6.  Back to cited text no. 11
Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 1982;39:461-74.  Back to cited text no. 12
NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: The idiopathic intracranial hypertension treatment trial. JAMA 2014;311:1641-51.  Back to cited text no. 13
Kalyvas AV, Hughes M, Koutsarnakis C, Moris D, Liakos F, Sakas DE, et al. Efficacy, complications and cost of surgical interventions for idiopathic intracranial hypertension: A systematic review of the literature. Acta Neurochir (Wien) 2017;159:33-49.  Back to cited text no. 14


  [Figure 1], [Figure 2]

  [Table 1]


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