Abstract
Central pontine myelinolysis (CPM) is a rare neurological complication reported in liver transplant recipients. A 16-year-old boy with Wilson disease underwent a living donor liver transplant for acute-on-chronic liver failure. On postoperative day 7, he was noted to have diplopia, dysphagia, and bilateral lower limb weakness with wide base gait with gradual progression to akinetic mutism. Magnetic resonance imaging (MRI) brain was performed which was suggestive of CPM, and it was attributed to tacrolimus. We stopped tacrolimus, and he was started on ciclosporin. His neurological symptoms started improving after 72 hours and he had a complete clinical recovery by 6 weeks. Repeat MRI brain at 16 weeks after liver transplantation showed complete radiological resolution of the pontine lesion.
To the Editor,
Central pontine myelinolysis (CPM) is a rare but serious neurological disorder occurring secondary to osmotic demyelination.1,2 A 16-year-old boy with Wilson disease presented with decompensated cirrhosis. He underwent a living donor liver transplantation (LT) with a right lobe graft with a graft recipient weight ratio of 1.18. Tacrolimus and steroid-based immunosuppression was started in the posttransplant period. Tacrolimus trough levels were 10 ng/dL on postoperative day (POD) 6. On POD 7, he developed diplopia secondary to left lateral rectus palsy, dysphagia, and bilateral lower limb proximal muscle weakness with wide base gait followed by akinetic mutism. Magnetic resonance imaging (MRI) of brain showed an ill-defined area of hyperintense signal on axial T2-weighted and fluid-attenuated inversion recovery images in the central pons, producing a “Mexican hat appearance” (Figure 1), characteristic of CPM. We attributed this to tacrolimus as he did not have other predisposing factors. Tacrolimus was replaced with ciclosporin, and he started to show clinical improvement after 72 hours. A complete neurological recovery was achieved in 6 weeks, and MRI showed resolution of the lesion (Figure 2). Tacrolimus was restarted after 6 months, which led to recurrence of neurological symptoms. The switch was again made to ciclosporin on which he is asymptomatic after 12 months of follow-up.
Figure 1.
A and B, Axial T2-weighted and fluid-attenuated inversion recovery (FLAIR) images show hyperintense signal in the central portion of pons (arrows). C, Axial diffusion weighted imaging shows restricted diffusion in the hyperintense areas.
Figure 2.
A, Axial T2-weighted images show persistent signal in the central portion of pons. B, Axial FLAIR images show central cavitation within the hyperintense signal. C, Axial diffusion weighted imaging shows interval resolution of diffusion restriction. Arrow shows central cavitation within the hyperintense signal.
CPM usually occurs in patients from 2 to 11 days after transplantation.3 The predisposing factors include malnutrition, Hepatic encephalopathy in the pre-LT period, and a rapid correction of hyponatremia in the perioperative period.3 Calcineurin inhibitors (CNIs) including ciclosporin and tacrolimus are also known to trigger CPM in the post-LT period.4,5 Patients with advanced liver disease and preexisting hepatic encephalopathy have a defective blood brain barrier and maladaptation of glial cells which makes their neurons susceptible to injury by CNI.6 CNI causes demyelination by its vasospastic effect due to reduced nitric oxide synthesis and also by inhibiting immunophilins.7 MRI with diffusion-weighted images is the modality of choice for early diagnosis of CPM.8 Prompt switching of one drug to the other (ciclosporin to tacrolimus and vice versa) or a different class of drug (e.g., mammalian target of rapamycin inhibitor) is recommended.9 In a previous report of tacrolimus-induced CPM in a pediatric liver recipient, a switch was made to rapamycin along with azathioprine, after which the patient became asymptomatic.10 Another report in an adult liver recipient mentions persistence of asymptomatic CPM 1 year after LT.11 Our patient was switched to ciclosporin after which his symptoms resolved both clinically and radiologically in 6 weeks.
Overall outcome of patients suffering from CPM is variable.8,2 In a previous series of 34 adult patients, only 33% had complete neurological recovery.12 Of all the CPM cases reported in pediatric liver recipients previously, 5 (50% mortality) were diagnosed in autopsy.2 Any patient with pseudobulbar signs or akinetic mutism in the post-LT period needs to have an urgent MRI of the brain to rule out CPM, as early recognition and proper intervention is helpful to prevent morbidity and mortality.
CRediT authorship contribution statement
Kinisha Patel: Conceptualization, data collection, Writing - original draft. Jagadeesh Menon: Conceptualization, Writing - review & editing. Naresh Shanmugam: Conceptualization, Writing - review & editing. Srinivasan Kalyanasundaram: Writing - review & editing. Mohamed Rela: Writing - review & editing, final approval for publication.
Conflicts of interest
The authors have none to declare.
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