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Neurologic Complications of Organ Transplantation Medication

  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
Updated: Feb 09, 2015

Medication Summary

Principles of medical therapy of neurologic complications in transplant patients are not altered by their transplant status. Nevertheless, additional attention must be paid to complex drug interactions and possible neurotoxicity so that the immunosuppression regimen and allograft function are not compromised.



Class Summary

Bacterial CNS infections are relatively uncommon in transplant recipients and are usually caused by opportunistic pathogens rare in immunocompetent individuals.

Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin)


Bactericidal activity against susceptible organisms.

Gentamicin (Garamycin, I-Gent, Jenamicin)


Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.

Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.

Amoxicillin (Amoxil)


Derivative of ampicillin and has similar antibacterial spectrum, namely certain gram-positive and gram-negative organisms. Superior bioavailability and stability to gastric acid and has broader spectrum of activity than penicillin. Somewhat less active than that of penicillin against Streptococcus pneumococcus. Penicillin-resistant strains also resistant to amoxicillin, but higher doses may be effective. More effective against gram-negative organisms (eg, N meningitidis, H influenzae) than penicillin. Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria.



Class Summary

Fungal CNS infections are frequently fatal in transplant recipients, and early diagnosis and initiation of treatment are of uttermost importance.

Amphotericin (Amphocin, Fungizone)


Polyene antibiotic produced by a strain of Streptomyces nodosus. Can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Liposomal preparation is more expensive but is associated with less nephrotoxicity.

Voriconazole (VFEND)


Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14-alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Also may be used in the treatment of coccidiosis and blastomycosis.


Antiviral agents

Class Summary

Viral CNS infections in immunosuppressed transplant recipients are caused by a variety of pathogens, and early treatment is essential.

Acyclovir (Zovirax)


Has affinity for viral thymidine kinase and once phosphorylated causes DNA chain termination when acted on by DNA polymerase.

Has demonstrated inhibitory activity against both HSV-1 and HSV-2. Selectively incorporated into infected cells.

Ganciclovir (Cytovene, Vitrasert)


Used in the treatment of viral infections with limited response to acyclovir, particularly with CMV infections.

Synthetic guanine derivative active against CMV. An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-infected cells.


Immunomodulatory agents

Class Summary

Agents with targeted immunotherapy are emerging treatment options that may find wider use in the near future.

Rituximab (Rituxan)


Rituximab has been used in the treatment of PTLD and refractory myasthenia in transplant recipients and in the treatment of paraproteinemic neuropathies in nontransplant patients.

Antibody genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Antibody is an IgG1 kappa immunoglobulin containing murine light and heavy chain variable region sequences and human constant region sequences.



Class Summary

Seizures in transplant recipients can be attributable to transient metabolic disturbances, drug neurotoxicity, focal CNS lesions, to the activation of a low seizure threshold, or to the exacerbation of a preexisting seizure disorder.

Long-term treatment with antiepileptic drugs (AEDs) may significantly complicate maintenance of immunosuppression because some AEDs (particularly phenytoin) may interfere with metabolism of cyclosporine and tacrolimus. Newer AEDs including topiramate, levetiracetam, and gabapentin seem to have a better adverse effect profile and may be better tolerated by transplant recipients.

Phenytoin (Dilantin)


First-line agent in the treatment of seizures and status epilepticus.

In transplant recipients, phenytoin may interfere with tacrolimus and cyclosporine metabolism.

Individualize dose. Administer larger dose before retiring if dose cannot be divided equally.

Fosphenytoin (Cerebyx)


Phenytoin derivative with better adverse effect profile.

Diphosphate ester salt of phenytoin, which acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin in turn stabilizes neuronal membranes and decreases seizure activity. To avoid need to perform molecular weight–based adjustments when converting between fosphenytoin and phenytoin sodium doses, express dose as phenytoin sodium equivalents (PE). Although can be administered IV and IM, IV route is route of choice and should be used in emergency situations.

Concomitant administration of an IV benzodiazepine is usually necessary to control status epilepticus. The antiepileptic effect of phenytoin, whether administered as fosphenytoin or parenteral phenytoin, is not immediate.

Midazolam (Versed)


Short-acting benzodiazepine used for sedation and treatment of refractory status epilepticus.

Because midazolam is water soluble, reaching peak EEG effects takes approximately 3 times longer than diazepam. Thus, the clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.

Lorazepam (Ativan)


First-line medication for immediate treatment of seizures and status epilepticus.

By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Important to monitor patient's blood pressure after administering dose. Adjust as necessary.

Propofol (Diprivan)


Used in treatment of refractory status epilepticus.

Phenolic compound unrelated to other types of anticonvulsants. Has general anesthetic properties when administered IV.

Levetiracetam (Keppra)


Used as adjunct therapy for partial seizures and myoclonic seizures. Also indicated for primary generalized tonic-clonic seizures. Mechanism of action is unknown. Useful in transplant patients as it has minimal drug-drug interactions.

Topiramate (Topamax)


Used as add-on therapy for partial seizures.

May be used in patients with hepatic impairment, but use is limited by lack of IV preparation.

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have a state-dependent sodium channel blocking action. Potentiates the inhibitory activity of GABA. May block glutamate activity. Not necessary to monitor topiramate plasma concentrations to optimize topiramate therapy. On occasions, addition of topiramate to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome.

Valproic acid (Depacon, Depakene, Depakote)


Because of potential hepatotoxicity, this drug is avoided in liver transplant recipients.

Chemically unrelated to other drugs that treat seizure disorders. Although the mechanism of action is not established, activity may be related to increased brain levels of GABA or enhanced GABA action. Valproate may also potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect. For conversion to monotherapy, concomitant AED dosage can ordinarily be reduced by approximately 25% q2wk. This reduction may start at initiation of therapy or be delayed by 1-2 wk if concern exists that seizures may occur with a reduction. Monitor patients closely during this period for increased seizure frequency.

As adjunctive therapy, divalproex sodium may be added to the patient's regimen at 10-15 mg/kg/d. May increase by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses < 60 mg/kg/d.

Contributor Information and Disclosures

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, Society for Neuroscience

Disclosure: Nothing to disclose.


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

  1. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN / SRTR 2010 Annual Data Report. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2011. Available at Accessed: May, 10, 2012.

  2. Zivkovic SA. Neurologic aspects of multiple organ transplantation. Handb Clin Neurol. 2014. 121:1305-17. [Medline].

  3. Patchell RA. Neurological complications of organ transplantation. Ann Neurol. 1994 Nov. 36(5):688-703. [Medline].

  4. Zivkovic S. Neuroimaging and neurologic complications after organ transplantation. J Neuroimaging. 2007 Apr. 17(2):110-23. [Medline].

  5. Zivkovic SA, Abdel-Hamid H. Neurologic manifestations of transplant complications. Neurol Clin. 2010 Feb. 28(1):235-51. [Medline].

  6. Neurologic complications in organ transplant recipients. Wijdicks EF, ed. Blue Books of Neurology. Oxford, England: Butterworth-Heinemann; 1999.

  7. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998 Jun 11. 338(24):1741-51. [Medline].

  8. Fishman JA. Infections in immunocompromised hosts and organ transplant recipients: essentials. Liver Transpl. 2011 Nov. 17 Suppl 3:S34-7. [Medline].

  9. Singh N, Husain S. Infections of the central nervous system in transplant recipients. Transpl Infect Dis. 2000 Sep. 2(3):101-11. [Medline].

  10. Potluri K, Holt D, Hou S. Neurologic complications in renal transplantation. Handb Clin Neurol. 2014. 121:1245-55. [Medline].

  11. Zierer A, Melby SJ, Voeller RK, Guthrie TJ, Al-Dadah AS, Meyers BF, et al. Significance of neurologic complications in the modern era of cardiac transplantation. Ann Thorac Surg. 2007 May. 83(5):1684-90. [Medline].

  12. Heroux A, Pamboukian SV. Neurologic aspects of heart transplantation. Handb Clin Neurol. 2014. 121:1229-36. [Medline].

  13. Zivkovic SA, Jumaa M, Barisic N, McCurry K. Neurologic complications following lung transplantation. J Neurol Sci. 2009 May 15. 280(1-2):90-3. [Medline].

  14. Wong M, Mallory GB, Goldstein J, et al. Neurologic complications of pediatric lung transplantation. Neurology. 1999 Oct 22. 53(7):1542-9. [Medline].

  15. Shigemura N, Sclabassi RJ, Bhama JK, Gries CJ, Crespo MM, Johnson B, et al. Early major neurologic complications after lung transplantation: incidence, risk factors, and outcome. Transplantation. 2013 Mar 27. 95(6):866-71. [Medline].

  16. Wigfield CH, Love RB. Clinical neurology in lung transplantation. Handb Clin Neurol. 2014. 121:1237-43. [Medline].

  17. Jacewicz M, Marino CR. Neurologic complications of pancreas and small bowel transplantation. Handb Clin Neurol. 2014. 121:1277-93. [Medline].

  18. Jacewicz M, Marino CR. Neurologic complications of pancreas and small bowel transplantation. Handb Clin Neurol. 2014. 121:1277-93. [Medline].

  19. Zivkovic SA. Neurologic complications after liver transplantation. World J Hepatol. 2013 Aug 27. 5(8):409-16. [Medline]. [Full Text].

  20. Wijdicks EF, Hocker SE. Neurologic complications of liver transplantation. Handb Clin Neurol. 2014. 121:1257-66. [Medline].

  21. Zivkovic SA, Eidelman BH, Bond G, Costa G, Abu-Elmagd KM. The clinical spectrum of neurologic disorders after intestinal and multivisceral transplantation. Clin Transplant. 2010 Mar-Apr. 24(2):164-8. [Medline].

  22. Giraldo M, Martin D, Colangelo J, Bueno J, Reyes J, Fung JJ, et al. Intestinal transplantation for patients with short gut syndrome and hypercoagulable states. Transplant Proc. 2000 Sep. 32(6):1223-4. [Medline].

  23. Stracciari A, Guarino M. Neurologic complications of intestinal transplantation. Handb Clin Neurol. 2014. 121:1267-76. [Medline].

  24. Rodriguez TE. Neurologic complications of bone marrow transplantation. Handb Clin Neurol. 2014. 121:1295-304. [Medline].

  25. Rodriguez TE. Neurologic complications of bone marrow transplantation. Handb Clin Neurol. 2014. 121:1295-304. [Medline].

  26. Grauer O, Wolff D, Bertz H, Greinix H, Kühl JS, Lawitschka A, et al. Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease. Brain. 2010 Oct. 133(10):2852-65. [Medline].

  27. Delios AM, Rosenblum M, Jakubowski AA, DeAngelis LM. Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease. J Neurooncol. 2012 Nov. 110(2):251-6. [Medline].

  28. Amato AA, Barohn RJ, Sahenk Z, Tutschka PJ, Mendell JR. Polyneuropathy complicating bone marrow and solid organ transplantation. Neurology. 1993 Aug. 43(8):1513-8. [Medline].

  29. Martín-Dávila P, Fortún J, López-Vélez R, Norman F, Montes de Oca M, Zamarrón P, et al. Transmission of tropical and geographically restricted infections during solid-organ transplantation. Clin Microbiol Rev. 2008 Jan. 21(1):60-96. [Medline].

  30. Srinivasan A, Burton EC, Kuehnert MJ. Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med. 2005 Mar 17. 352(11):1103-11. [Medline].

  31. Schiff D, O'Neill B, Wijdicks E, Antin JH, Wen PY. Gliomas arising in organ transplant recipients: an unrecognized complication of transplantation?. Neurology. 2001 Oct 23. 57(8):1486-8. [Medline].

  32. Jacobson CA, LaCasce AS. Lymphoma: risk and response after solid organ transplant. Oncology (Williston Park). 2010 Sep. 24(10):936-44. [Medline].

  33. Campellone JV, Lacomis D, Kramer DJ, et al. Acute myopathy after liver transplantation. Neurology. 1998 Jan. 50(1):46-53. [Medline].

  34. Lacomis D. Neuromuscular disorders in critically ill patients: review and update. J Clin Neuromuscul Dis. 2011 Jun. 12(4):197-218. [Medline].

  35. Wijdicks EF, Litchy WJ, Wiesner RH, Krom RA. Neuromuscular complications associated with liver transplantation. Muscle Nerve. 1996 Jun. 19(6):696-700. [Medline].

  36. Dyck PJ, Velosa JA, Pach JM, et al. Increased weakness after pancreas and kidney transplantation. Transplantation. 2001 Oct 27. 72(8):1403-8. [Medline].

  37. Lichtenstein GR, Yang YX, Nunes FA, Lewis JD, Tuchman M, Tino G, et al. Fatal hyperammonemia after orthotopic lung transplantation. Ann Intern Med. 2000 Feb 15. 132(4):283-7. [Medline].

  38. Sun HY, Singh N. Opportunistic infection-associated immune reconstitution syndrome in transplant recipients. Clin Infect Dis. 2011 Jul 15. 53(2):168-76. [Medline].

  39. Bodkin CL, Eidelman BH. Sirolimus-induced posterior reversible encephalopathy. Neurology. 2007 Jun 5. 68(23):2039-40. [Medline].

  40. Bronster DJ, Emre S, Boccagni P, et al. Central nervous system complications in liver transplant recipients--incidence, timing, and long-term follow-up. Clin Transplant. 2000 Feb. 14(1):1-7. [Medline].

  41. Buis CI, Wiesner RH, Krom RA, et al. Acute confusional state following liver transplantation for alcoholic liver disease. Neurology. 2002 Aug 27. 59(4):601-5. [Medline].

  42. Chabolla DR, Wszolek ZK. Pharmacologic management of seizures in organ transplant. Neurology. 2006 Dec 26. 67(12 Suppl 4):S34-8. [Medline].

  43. Coplin WM, Cochran MS, Levine SR, Crawford SW. Stroke after bone marrow transplantation: frequency, aetiology and outcome. Brain. 2001 May. 124(Pt 5):1043-51. [Medline].

  44. Eidelman BH, Abu-Elmagd K, Wilson J, et al. Neurologic complications of FK 506. Transplant Proc. 1991 Dec. 23(6):3175-8. [Medline].

  45. Heroux A, Pamboukian SV. Neurologic aspects of heart transplantation. Handb Clin Neurol. 2014. 121:1229-36. [Medline].

  46. Kamar N, Bendall RP, Peron JM, Cintas P, Prudhomme L, Mansuy JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. 2011 Feb. 17(2):173-9. [Medline]. [Full Text].

  47. Kleinschmidt-DeMasters BK, Marder BA, Levi ME, et al. Naturally acquired West Nile virus encephalomyelitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features. Arch Neurol. 2004 Aug. 61(8):1210-20. [Medline].

  48. Lewis MB, Howdle PD. Neurologic complications of liver transplantation in adults. Neurology. 2003 Nov 11. 61(9):1174-8. [Medline].

  49. Martinez AJ. The neuropathology of organ transplantation: comparison and contrast in 500 patients. Pathol Res Pract. 1998. 194(7):473-86. [Medline].

  50. Mendez O, Kanal E, Abu-Elmagd KM. Granulomatous amebic encephalitis in a multivisceral transplant recipient. Eur J Neurol. 2006 Mar. 13(3):292-5. [Medline].

  51. Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf. 2000 Aug. 23(2):101-13. [Medline].

  52. Schwartz S, Ruhnke M, Ribaud P. Improved outcome in central nervous system aspergillosis, using voriconazoletreatment. Blood. 2005 Oct 15. 106(8):2641-5. [Medline].

  53. Sutcliffe RP, Maguire DD, Muiesan P, Dhawan A, Mieli-Vergani G, O'Grady JG. Liver transplantation for Wilson's disease: long-term results and quality-of-life assessment. Transplantation. 2003 Apr 15. 75(7):1003-6. [Medline].

  54. Wijdicks EF. Impaired consciousness after liver transplantation. Liver Transpl Surg. 1995 Sep. 1(5):329-34. [Medline].

  55. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression. Neurology. 1995 Nov. 45(11):1962-4. [Medline].

  56. Zivkovic SA. Neurologic aspects of multiple organ transplantation. Handb Clin Neurol. 2014. 121:1305-17. [Medline].

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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