Central Nervous System Complications After Transplantation
Section snippets
Incidence
The frequency at which patients experience neurologic complications after organ or bone marrow transplants has been reviewed in several studies.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 However, most are retrospective and have not used rigorous definitions of specific complications, meaning that at best they represent broad approximations of incidence and likely underestimate less severe sequelae. Studies included in Table 2 were restricted to contemporary clinical
Failure to awaken
When a patient does not recover normal alertness after transplant surgery, a review of operative and perioperative factors often reveals relevant abnormalities. The operative records should be reviewed for evidence of hypotension (related to excess blood loss, cardiac arrhythmias or cardiac arrest, time on cardiac bypass, and postreperfusion syndrome in liver transplantation22). Air embolism can also occur during organ or vascular manipulation and may present with perioperative mental status
Encephalopathy
Alterations in awareness and arousal are frequent after transplantation, most occurring in the first 30 days postoperatively.11 The spectrum of encephalopathy encompasses reduced levels of consciousness as severe as coma to delirium with diminished attention, or agitation and hallucinations.37 The differential diagnosis of altered mentation after transplantation is shown in Table 3; many cases are multifactorial. The prognosis for patients with encephalopathy is largely governed by the
Akinetic mutism
A state of impaired verbal and motor responsiveness has been noted in transplant recipients.23 Patients appear awake but do not speak and have minimal motor activity. This syndrome has been reported as a complication of cyclosporine and tacrolimus toxicity, improving after drug discontinuation,41 but may also be seen with CPM or HIE.42 A similar picture has been reported with amphotericin treatment of HSCT patients who received irradiation as part of conditioning.43, 44 Radiation may open the
Seizures
Seizures are not only frightening to a patient, their family, and health care personnel, but they can lead to patient injury, hemodynamic instability, risk of aspiration, and dislodgement of catheters and monitoring devices. Contemporary series have revealed that seizures still occur in 5% to 10% of transplant patients, most often in the first few weeks (see Table 1). Many of the same processes listed in Table 3 may also present with seizures, often associated with prodromal or postictal
Drug toxicity
The introduction of cyclosporine and subsequently other effective immunosuppressive agents revolutionized transplantation, minimizing rejection and improving graft survival.59 Induction agents are sometimes used immediately after transplant (including thymoglobulin, OKT3, or basiliximab) followed by maintenance therapy with a calcineurin inhibitor (CNI) (cyclosporine or tacrolimus) often coupled with mycophenolate mofetil (MMF) and corticosteroids. CNIs and MMF are usually continued after
CPM
CPM was first described in malnourished alcoholics experiencing rapid increases in serum sodium and osmolality.96 It is now categorized under the rubric osmotic demyelination syndromes (ODSs),97 because shifts in sodium and brain water are postulated to result in noninflammatory oligodendrocyte injury and intramyelin edema. This situation results in myelin loss, particularly within the central pons, but involvement of other brain regions (including the basal ganglia, external capsule, and
Stroke
Development of focal neurologic deficits in a transplant patient most often signals a vascular or infectious CNS process. However, focal deficits may also be seen after seizures (ie, postictal Todd paresis), with drug neurotoxicity (ie, asymmetric RPLE) and with peripheral nerve dysfunction (eg, related to herpes zoster reactivation or perioperative compression neuropathy). Conversely, not infrequently focal and multifocal CNS lesions in transplant patients present with only nonfocal mental
HSCT and GVHD
HSCT involves transfer of stem cells from 1 person to another (allogeneic) or (after procurement and storage) back to the donor (autologous).110 This process allows reconstitution of marrow and immune function after ablation of native bone marrow (and it is hoped the underlying disease process or malignancy) with toxic myeloablative conditioning regimens (typically involving a combination of cyclophosphamide and total-body irradiation [TBI]). However, without hematopoiesis or immune function
Idiopathic hyperammonemia
A rare but often fatal syndrome has been described in 0.5% of HSCT recipients during the period of severe neutropenia.124 Onset is acute, with lethargy, confusion, and tachypnea, usually progressing to seizures and coma. Ammonia levels are characteristically increased (often more than 200 μmol/L), associated with respiratory alkalosis, but normal or only mildly increased liver enzyme levels. Brain imaging may reveal marked cerebral edema, similar to Reye syndrome.125 Urea cycle defects
CNS posttransplantation lymphoproliferative disorder
Lymphoma is the most common brain tumor seen in transplant recipients. The CNS may be the primary site of involvement or associated with systemic posttransplantation lymphoproliferative disorder (PTLD).128 Most cases of PTLD are associated with Epstein-Barr virus (EBV) infection and occur a few years after solid organ transplantation (although some may occur within the first year).129 Tumor involvement is more often parenchymal than leptomeningeal (a pattern similar to that seen in patients
CNS infections
More potent and effective immunosuppressive regimens have reduced the risk of graft rejection but increased the susceptibility of transplant recipients to a variety of opportunistic CNS infections. Furthermore, because of the blunted host immune response and less pathogenic nature of these organisms, presentation of these potentially life-threatening infections may be nonspecific and far from acute or obvious. Headache and low-grade fever may be the only signs of CNS involvement, whereas mental
Summary
Neurologic complications contribute to significant morbidity after solid organ transplant and HSCT. Encephalopathy is the most common neurologic presentation in the early posttransplant period and may be related to serious organ or graft dysfunction, drug neurotoxicity, or CNS lesions (including vascular, infectious, or demyelinating). Mental status changes may be accompanied by seizures, which are especially common in the setting of immunosuppressant drug toxicity causing RPLE. Prognosis for
References (135)
- et al.
Quality of life after liver transplantation. A systematic review
J Hepatol
(2008) - et al.
Incidence of and risk factors for neurologic complications after heart transplantation
Transplant Proc
(2005) - et al.
Significance of neurologic complications in the modern era of cardiac transplantation
Ann Thorac Surg
(2007) - et al.
Neurologic complications following lung transplantation
J Neurol Sci
(2009) - et al.
Neurological complications following adult lung transplantation
Am J Transplant
(2010) - et al.
Neurological complications in liver transplantation
Transplant Proc
(1999) - et al.
Severe neurological events following liver transplantation
Arch Med Res
(2007) - et al.
Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance
Biol Blood Marrow Transplant
(2007) - et al.
Postreperfusion syndrome: hypotension after reperfusion of the transplanted liver
J Crit Care
(1993) - et al.
Extracorporeal membrane oxygenation in primary graft failure after heart transplantation
Ann Thorac Surg
(2010)
A model to predict the development of mental status changes of unclear cause after liver transplantation
Liver Transpl
Rejection encephalopathy
Lancet
Neuropsychiatric complications of liver and other solid organ transplantation
Liver Transpl
Neurological complications following liver transplantation
Lancet
Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema?
J Hepatol
Uremic encephalopathies: clinical, biochemical, and experimental features
Am J Kidney Dis
Cyclosporin A in patients receiving renal allografts from cadaver donors
Lancet
Severe central-nervous-system toxicity associated with cyclosporin
Lancet
The mechanism of action of cyclosporin A and FK506
Clin Immunol Immunopathol
Tacrolimus-related neurologic and renal complications in liver transplantation: a single-center experience
Transplant Proc
Cyclosporin metabolites and neurotoxicity
Lancet
A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation
J Heart Lung Transplant
No major neurologic complications with sirolimus use in heart transplant recipients
Mayo Clin Proc
Tacrolimus-related seizure in the early postoperative period after liver transplantation
Transplant Proc
Sirolimus in liver transplant recipients: a large single-center experience
Transplant Proc
Persistent cortical blindness after cyclosporine leukoencephalopathy
Liver Transpl Surg
Osmotic demyelination syndrome
Am J Med Sci
Contrasting the neurologic complications of cardiac transplantation in adults and children
J Child Neurol
Effect of neurologic complications on outcome after heart transplant
Arch Neurol
Infectious and non-infectious neurologic complications in heart transplant recipients
Medicine (Baltimore)
Central nervous system complications after lung transplantation
J Heart Lung Transplant
Central nervous system complications in liver transplant recipients–incidence, timing, and long-term follow-up
Clin Transplant
Neurological complications of liver transplantation in adults
Neurology
Perioperative neurological complications after liver transplantation are best predicted by pre-transplant hepatic encephalopathy
Neurocrit Care
The clinical spectrum of neurologic disorders after intestinal and multivisceral transplantation
Clin Transplant
Neurologic complications after renal transplant
Exp Clin Transplant
Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukemia: a comparative study
Neurology
Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study
Neurology
Prospective evaluation of neurological complications after allogeneic bone marrow transplantation
Neurology
Spectrum and prognosis of neurologic complications after hematopoietic transplantation
Neurology
Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus
Ann Surg
Central nervous system lesions in adult liver transplant recipients: clinical review with implications for management
Medicine (Baltimore)
Organ survival after primary dysfunction of liver grafts in clinical orthotopic liver transplantation
Transpl Int
Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience
Clin Transplant
Neuropathology of liver transplantation
Clin Neuropathol
The neuropathology of cardiac allograft transplantation. An autopsy series of 18 patients
Arch Pathol Lab Med
The neuropathology of orthotopic liver transplantation: an autopsy series of 16 patients
Arch Pathol Lab Med
The neuropathology of intestinal failure and small bowel transplantation
Acta Neuropathol
Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature
Crit Care Med
The encephalopathy associated with septic illness
Clin Invest Med
Cited by (29)
Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study
2022, Journal of InfectionCitation Excerpt :Finally, high-quality evidence to guide the best therapeutic approach to CNS infections specifically in SOT recipients is lacking. Of note, management is often complicated by potential drug toxicities and drug-drug interactions between antimicrobial and immunosuppressive drugs3. Increasing our knowledge on the current epidemiology and clinical presentations of CNS infections in SOT recipients is essential to improve diagnostic, preventive, and therapeutic approaches in this specific group of patients.
Complications of Solid Organ Transplantation: Cardiovascular, Neurologic, Renal, and Gastrointestinal
2019, Critical Care ClinicsCitation Excerpt :Seizures are a common postoperative neurologic complication, recognized in approximately 5% to 10% of all transplant patients. The causes are related to many of the problems already addressed, including immunosuppression toxicity, metabolic derangements, infections, stroke, and malignancy.70,83 Seizures due to CNIs have been described and are usually generalized.84
Neurologic Complications of Solid Organ Transplantation
2017, Neurologic ClinicsThe immunologic considerations in human head transplantation
2017, International Journal of SurgeryCitation Excerpt :It must be recognized that even after commonly performed organ transplantation, neurological complications occur in the 25%–35% range [42,43]. The most common neurological problem is neurotoxicity [44] frequently due to CNIs since calcineurin is expressed in several areas of the brain and is a major regulator of key proteins essential for synaptic transmission and neuronal excitability, involved in memory and synaptic plasticity [45]. Central Neurotoxicity from these drugs, at therapeutic or high levels, can occur both late and early.
Neurologic complications of transplantation
2017, Handbook of Clinical NeurologyNeuropsychiatric Complications
2015, Transplantation of the Liver: Third Edition
The authors have nothing to disclose.