Background

Organ transplantation has developed at an incredibly rapid pace since its introduction in the 1950s, and it has become a life-saving procedure for patients with end-stage organ failure. In 2009, more than 20,000 hematopoietic stem cell transplantations and 27,000 solid organ transplantations were performed in the United States alone.^[1]. Complex multiorgan failure may require simultaneous transplantation of several organs. A combined multiorgan transplantation approach may offer a lower rate of allograft rejection and lower immunosuppression needs.^[2]

The posttransplantation clinical course is generally complicated by dysfunction of various organ systems, and early or delayed neurologic complications may develop in 30–60% of patients.^{[3, 4, 5, 6, 2, 7, 8, 9]}Because of the constantly changing protocols of transplantation and immunosuppression, the nature of neurologic complications has changed over time. Improved survival of patients undergoing transplant also shifts the focus of neurologic complications towards long-term complications. Nevertheless, diagnosis and management of perioperative complications of organ transplantation still plays a prominent role in determining the postoperative course of allograft recipients.

Organ transplantation may also improve neurologic function in various disorders with neurologic manifestations such as Wilson disease (liver transplantation), familial amyloidosis with neuropathy (liver transplantation), and diabetic neuropathy (pancreas transplantation).

Future developments in the field of organ transplantation, including newer immunosuppressive medications and xenograft, pluripotent stem cell and neural tissue transplantation, will further change the spectrum of neurologic and other complications in transplant recipients.

Pathophysiology

Neurologic complications are related to the surgical procedure of transplantation, posttransplant immunosuppression, opportunistic infection, or the inherent disorders that led to transplantation.

Some neurologic complications of transplant surgery are inherent to all transplant types (eg, opportunistic CNS infections, immunosuppressant neurotoxicity, anoxic encephalopathy), while others are more common with certain types of allografts.

Posttransplant immunosuppression increases the risk of opportunistic infections, particularly after 1 month posttransplantation.^{[10, 11]}While greater immunosuppression increases the risk of opportunistic infections and immunosuppressant neurotoxicity, it may be needed for treatment of allograft rejection. Exposure of patients undergoing transplant to endemic pathogens may result in increased frequency of certain infections.

The variety of conditions that led to organ failure requiring transplantation may also be associated with neurologic complications, including amyloid and diabetic neuropathy. Delayed allograft function may also precipitate various complications, including impairment of consciousness with hepatic and uremic encephalopathy.

Frequency

Neurologic complications affect up to 30–60% of allograft recipients.

Neurologic complications of organ transplantation occur internationally with a similar frequency as in the United States.

Because the spectrum of CNS infectious pathogens depends on exposure, some endemic pathogens, mucormycosis, and parasitic diseases may be more common in tropical regions.

Mortality/Morbidity

Neurologic complications in patients undergoing transplant complicate posttransplant recovery, and opportunistic CNS infections may be very difficult to treat in patients who are immunosuppressed. Opportunistic CNS infections affect 1–3% of transplant patients, with a reported mortality rate of 75–90%.^[12]

Clinical Presentation

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Media Gallery

Neurotoxicity of calcineurin inhibitors manifests on MRI with predominantly posterior hyperintensities on T2-weighted and FLAIR imaging sequences (FLAIR; TE 175.0, TR 9002).
Muscle cryostat section at pH 4.6 shows decreased ATPase reactivity with reduced (arrows) and absent (asterisk) muscle fiber staining in critical illness myopathy (courtesy of Dr David Lacomis).

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Author

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Neurological Association, American Society of Neurorehabilitation, American Academy of Neurology, American Heart Association, American Medical Association, National Stroke Association, Phi Beta Kappa, Tennessee Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Norman C Reynolds, Jr, MD Neurologist, Veterans Affairs Medical Center of Milwaukee; Clinical Professor, Medical College of Wisconsin

Norman C Reynolds, Jr, MD is a member of the following medical societies: American Academy of Neurology, Association of Military Surgeons of the US, International Parkinson and Movement Disorder Society, Sigma Xi, The Scientific Research Honor Society, Society for Neuroscience

Disclosure: Nothing to disclose.

Acknowledgements

Sasa Zivkovic, MD, PhD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, University of Pittsburgh and VA Pittsburgh Healthcare System

Sasa Zivkovic, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Peripheral Nerve Society

Disclosure: Baxter Bioscience Meeting attendance expenses Attendee