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Neurologic Complications of Organ Transplantation Workup

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

Laboratory Studies

See the list below:

  • Cerebrospinal fluid (CSF) studies: CSF analysis is essential in investigations of neurologic complications and possible opportunistic CNS infections in transplant recipients who are immunosuppressed.
    • Cell count and differential, protein, glucose
    • Microbiology - Gram stain, Ziehl-Nielsen acid-fast stain, India ink, and bacterial, viral, fungal, and mycobacterial cultures
    • Molecular studies - Polymerase chain reaction (PCR) for herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), EBV, human herpesvirus 6 (HHV-6), hepatitis E (HEV), measles virus, BK/JC virus, West Nile virus (WNV), and mycobacteria; PCR for EBV in patients with suspected PTLD
    • Immunology studies - Cryptococcal antigen, toxoplasma titers, syphilis tests (ie, microhemagglutination treponemal test [MHA-TP], fluorescent treponemal antibody absorbed test [FTA-ABS], venereal disease research laboratory [VDRL]), viral antibody titers (ie, HSV, VZV, HHV-6, EBV, CMV, WNV), histoplasma and mucor titers, and histoplasma and aspergillus antigens
    • Pathology - CSF cytology and flow cytometry, which are helpful in evaluation of possible PTLD
  • Other tests: Neurologic complications of transplantation mostly stem from underlying disorders that led to transplant, transplant procedures, and immunosuppression, and a variety of laboratory tests are helpful in establishing the cause of these complications.
    • Complete blood cell count and differential
    • Electrolytes, blood urea nitrogen, creatinine, magnesium, calcium and glucose, liver function tests, ammonia level, and thyroid-stimulating hormone (TSH) helpful in investigations of altered consciousness
    • Vitamins B-1, B-6, B-12, E, folic acid, homocysteine, and metyhlmalonic acid because many transplant recipients develop nutritional deficiencies
    • Urinalysis, urine cryptococcal antigen, and urine, blood, and sputum cultures because systemic infection may cause septic encephalopathy
    • Drug levels (note that neurotoxicity may occur even within therapeutic ranges of drug levels)
      • Immunosuppressive medications (eg, tacrolimus, cyclosporine)
      • Other medications (eg, phenytoin, valproate)
    • Creatine kinase (CK) is helpful in evaluation of toxic or inflammatory myopathy (may be within the reference range in critical illness myopathy after 2 wk)

Imaging Studies

See the list below:

  • Neuroimaging studies have a significant role in evaluation of neurologic posttransplant complications because they can provide important evidence on focal or diffuse nervous system injury.
  • CT scanning of the head is helpful when MRI is not immediately available, and it is sensitive for detection of intracranial hemorrhage. Cranial CT scanning may also confirm whether proceeding with lumbar puncture is safe. CT scanning of the sinuses can be used to evaluate opportunistic fungal sinus infections that may extend to the CNS.
  • Cranial MRI with and without gadolinium contrast is an essential diagnostic tool in the evaluation of transplant recipients with impaired consciousness or with focal findings. Cranial MRI findings may determine further diagnostic steps and possible therapeutic interventions. Diffusion-weighted imaging (DWI) and fluid-attenuated inversion-recovery (FLAIR) sequence images should be included in a standard protocol.
  • Magnetic resonance venography (MRV) is helpful in evaluation of possible cerebral venous sinus thrombosis.
  • MRI of the spine with and without contrast is helpful in the evaluation of epidural abscesses and other causes of myelopathy and radiculopathy.

Other Tests

See the list below:

  • EEG is indispensable in the evaluation of possible seizures and impairment of consciousness. It is necessary for establishing the diagnosis of nonconvulsive status epilepticus, and findings are crucial for differentiating metabolic encephalopathy from complex partial seizures. Certain features of EEG, including generalized slowing, are suggestive of metabolic encephalopathy, and triphasic waves are highly suggestive of uremic and hepatic encephalopathy. Prolonged continuous monitoring may be needed in patients with refractory seizures to titrate therapy.
  • Nerve conduction and electromyography studies (NCS/EMG) are very helpful in evaluation of focal weakness and possible perioperative neuropathies, critical illness myopathy/polyneuropathy, and other neuromuscular disorders. Studies in ICU setting may be technically limited. In patients with indwelling catheters, electrical safety risks of proximal nerve stimulation should be assessed. Needle electromyography may be limited in patients with coagulopathy. Direct muscle needle stimulation may be helpful to demonstrate inexcitability of muscle in critical illness myopathy.
  • Echocardiography (transthoracic or transesophageal) is used to determine the presence of intracardiac clots and nonbacterial thrombotic or infective endocarditis.


See the list below:

  • Lumbar puncture may be indicated if it can be performed safely. It is indispensable in evaluation of possible opportunistic CNS infections.
  • Nerve and muscle biopsy is rarely used in transplant patients. It is helpful to document lymphoproliferative disorders involving nerve or muscle. Muscle biopsy (needle or open) may be helpful to document critical illness myopathy.{{Imagenum2:2122992
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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