An Uncommon Neurologic Complication Following Orthotopic Liver Transplantation


American Journal of Transplantation Images in Transplantation – Continuing Medical Education (CME)

Each month, the American Journal of Transplantation will feature Images in Transplantation, a journal-based CME activity, chosen to educate participants on current developments in the science and imaging of transplantation. Participants can earn 1 AMA PRA Category 1 Credit™ per article at their own pace.

This month's feature article is titled: “An Uncommon Neurologic Complication Following Orthotopic Liver Transplantation.”

Accreditation and Designation Statement

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Blackwell Futura Media Services, the American Society of Transplant Surgeons and the American Society of Transplantation. Blackwell Futura Media Services is accredited by the ACCME to provide continuing medical education for physicians.

Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Statement of Need

Central nervous system impairment is a major source of morbidity, mortality and expense after orthotopic liver transplantation. Neurologic complications have been reported to occur in 8%–47% of transplant recipients. The most common encountered derangements include encephalopathy, seizures, infections, immunosuppressive drug-related complications, and cerebral hemorrhage. However other rare entities must be considered.

Purpose of Activity

The purpose is to improve competency in timely diagnosis and initiation of appropriate therapeutic intervention for patients with central nervous system impairment in liver transplant recipients.

Identification of Practice Gap

Neurologic complications after orthotopic liver transplant are common. Due to similar clinical presentations, rarer neurologic complications must be considered. Correct diagnosis of neurologic impairment will allow for appropriate therapy.

Learning Objectives

Upon completion of this educational activity, participants will be able to:

  • Examine clinical and radiological evidence to diagnose this rare neurologic impairment after orthotopic liver transplant.
  • Identify patient factors that may predispose to an uncommon neurologic impairment post–orthotopic liver transplantation.
  • Understand the current theory of pathogenesis for this rare neurologic syndrome post–orthotopic liver transplantation.
  • Determine appropriate treatment for patients with rare neurological impairment.

Target Audience

This activity has been designed to meet the educational needs of physicians and surgeons in the field of transplantation.


No commercial support has been accepted related to the development or publication of this activity. Blackwell Futura Media Services has reviewed all disclosures and resolved or managed all identified conflicts of interest, as applicable.


Allan D. Kirk, MD, PhD, FACS, has no relevant financial relationships to disclose.


Sandy Feng, MD, PhD, discloses stock and/or equity interest in Abbott, Amgen, Charles River Labs, Eli Lily, Glaxo-Smith-Klein, Hospira, Johnson & Johnson, Express Scripts, Medco, Merck, Pfizer, and Stryker; research support from Cumberland and Quark; and research support and consulting work for Novartis.

Douglas W. Hanto, MD, PhD, has no relevant financial relationships to disclose.


G. Swope Munday, MD, Mary Eng, MD, Fred Klink, MD, and Christopher M. Jones, MD, have no relevant financial relationships to disclose.

ASTS Staff

Mina Behari, Director of Education, has no relevant financial relationships to disclose.

This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by the American Journal of Transplantation. The peer reviewers have no relevant financial relationships to disclose. The peer review process for the American Journal of Transplantation is blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.

Instructions on Receiving CME Credit

This activity is designed to be completed within an hour. Physicians should claim only those credits that reflect the time actually spent in the activity. This activity will be available for CME credit for twelve months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional twelve months.

Follow these steps to participate, answer the questions and claim your CME credit:

  • Log on to
  • Read the learning objectives, target audience, and activity disclosures.
  • Read the article in print or online format.
  • Reflect on the article.
  • Access the CME Exam, and choose the best answer to each question.
  • Complete the required evaluation and print your CME certificate.

An Uncommon Neurologic Complication Following Orthotopic Liver Transplantation

The patient is a 58-year-old female with hepatitis C cirrhosis who was admitted to the hospital for encephalopathy with Model for End-stage Liver Disease (MELD) score of 31 (bilirubin 15.2 mg/dL, creatinine 2.72 mg/dL, INR 2.21) and serum sodium 119 mmol/L. Hyponatremia was treated with fluid restriction and encephalopathy improved. Five days later, with a serum sodium of 132 mmol/L, she underwent an uneventful orthotopic liver transplant. The patient had no intraoperative instability and received eight units of blood.

On postoperative day (POD) 1, she was extubated and neurologically intact. Serum sodium was 140 mmol/L. Postoperatively she received a steroid taper, initiated mycophenolate mofetil 1 g twice daily and tacrolimus 2 mg daily was started POD 3. Sodium values POD 1–4 were 140, 142, 142, and 147 mmol/L, respectively.

On POD 5, her sodium peaked at 154 mmol/L and she developed tremors and nystagmus. Immunosuppression included mycophenalate mofetil 1 g twice daily, methylprednisolone 20 mg daily and tacrolimus level of 7.7. Her neurologic status deteriorated further and by POD 7, she exhibited no eye opening and was unresponsive to verbal and painful stimuli. Immunosuppressants were held, and infectious work-up and head CT (Figure 1) were negative. Sodium corrected to 142 mmol/L over the next two days, and her clinical picture became one of “locked-in” syndrome. Brain MRI was obtained (Figures 2 & 3).

Figure 1.

Axial unenhanced computed tomography of the head obtained at the level of the fourth ventricle shows a symmetric, centrally located region with normal attenuation within the pons (arrow). No suspicious lesions or active disease is appreciated.

Figure 2.

Sagittal fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) image at the level of the pons. T1 prologation reveals a symmetric region of low signal involving the basilar pons (arrow A) with sparing of the descending corticospinal tracts (arrow B).

Figure 3.

Axial fluid-attenuated inversion recovery (FLAIR) MR image shows a bat wing–shaped area of T2 prolongation surrounding an area of encephalomalacia in the central pons.

Airway was maintained, however she required enteral access. After 3 months of intensive speech, occupational and physical therapy, she showed gradual neurological improvement, but continued to demonstrate aphasia and mild ataxia.

G. S. Munday1, M. Eng1, F. Klink2 and C. M. Jones1,*

1Hiram C. Polk, Jr, MD Department of Surgery, Division of Transplantation, University of Louisville, Louisville, KY

2Radiologist Specialists of Louisville, Jewish Hospital, Louisville, KY

*Corresponding author: Christopher M. Jones,


  1. What neuronal cell is most directly affected during pathogenesis of this patient's condition?
    1. neurons
    2. astrocytes
    3. oligodendrocytes
    4. ependymal cells
    5. Schwann cells
  2. Which of the following patient factors least likely predisposes a patient to developing this condition?
    1. SIADH
    2. end-stage renal disease
    3. liver disease
    4. morbid obesity
    5. chronic alcohol abuse
  3. How soon after the development of symptoms are classic central pontine myelinolysis (CPM) lesions visible on MRI?
    1. 6 to 12 hours
    2. 12 to 24 hours
    3. 3 to 5 days
    4. 7 to 14 days
    5. 14 to 28 days
  4. Which antirejection/immunosuppressive agent has most often been associated with cases of CPM?
    1. mycophenolate
    2. prednisone
    3. cyclosporine
    4. tacrolimus
    5. rapamycin
  5. Which of the following therapies is the treatment of choice for CPM?
    1. normalizing electrolyte imbalances
    2. supportive care in intensive care unit
    3. intravenous immunoglobulins
    4. plasmapheresis
    5. increased target trough of calcineurin inhibitor

To complete this activity and earn credit, please go to