eMedicine Specialties > Neurology > Critical Care Neurology

Neurologic Complications of Organ Transplantation: Differential Diagnoses & Workup

Author: Sasa Zivkovic, MD, MSc, Assistant Professor, Department of Neurology, Division of Neuromuscular Diseases, University of Pittsburgh and VA Pittsburgh Healthcare System
Contributor Information and Disclosures

Updated: Jan 25, 2008

Differential Diagnoses

Acute Inflammatory Demyelinating Polyradiculoneuropathy
Neurological Sequelae of Infectious Endocarditis
Acute Stroke Management
Primary CNS Lymphoma
Cardioembolic Stroke
Spinal Cord Infarction
Cerebral Venous Thrombosis
Spinal Epidural Abscess
Epidural Hematoma
Status Epilepticus
Epilepsia Partialis Continua
Subdural Hematoma
Femoral Mononeuropathy
Uremic Encephalopathy
Focal Status Epilepticus
Viral Encephalitis
Herpes Simplex Encephalitis
Viral Meningitis
Intracranial Hemorrhage
Vitamin B-12 Associated Neurological Diseases

Other Problems to Be Considered

Anoxic encephalopathy
Hepatic encephalopathy
Critical illness myopathy
Critical illness polyneuropathy
Fungal meningitis
GVHD
Central pontine myelinolysis

Workup

Laboratory Studies

  • 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), 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, and folic 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) helpful in evaluation of inflammatory myopathy (may be within the reference range in critical illness myopathy after 2 wk)

Imaging Studies

  • 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

  • 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.

Procedures

  • 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.

More on Neurologic Complications of Organ Transplantation

Overview: Neurologic Complications of Organ Transplantation
Differential Diagnoses & Workup: Neurologic Complications of Organ Transplantation
Treatment & Medication: Neurologic Complications of Organ Transplantation
Follow-up: Neurologic Complications of Organ Transplantation
Multimedia: Neurologic Complications of Organ Transplantation
References
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Further Reading

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Keywords

opportunistic infection, immunosuppression, central nervous system infection, CNS infection, organ transplant, solid organ transplantation, kidney transplantation, liver transplantation, heart transplantation, lung transplantation, intestinal transplantation, posttransplant immunosuppression, opportunistic infection

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Contributor Information and Disclosures

Author

Sasa Zivkovic, MD, MSc, Assistant Professor, Department of Neurology, Division of Neuromuscular Diseases, University of Pittsburgh and VA Pittsburgh Healthcare System
Sasa Zivkovic, MD, MSc is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

Medical Editor

Norman C Reynolds Jr, MD, Professor, Department of Neurology, Medical College of Wisconsin
Norman C Reynolds Jr, MD is a member of the following medical societies: American Academy of Neurology, American Chemical Society, American Clinical Neurophysiology Society, Association of Military Surgeons of the US, Movement Disorders Society, Sigma Xi, and Society for Neuroscience
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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 Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Novartis Consulting fee Review panel membership

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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