Elsevier

Neurologic Clinics

Volume 29, Issue 4, November 2011, Pages 943-972
Neurologic Clinics

Central Nervous System Complications After Transplantation

https://doi.org/10.1016/j.ncl.2011.07.002Get rights and content

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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

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