Neurologic Complications of Transplantation

Abstract

Neurologic disturbances including encephalopathy, seizures, and focal deficits complicate the course 10-30% of patients undergoing organ or stem cell transplantation. While much or this morbidity is multifactorial and often associated with extra-cerebral dysfunction (e.g., graft dysfunction, metabolic derangements), immunosuppressive drugs also contribute significantly. This can either be through direct toxicity (e.g., posterior reversible encephalopathy syndrome from calcineurin inhibitors such as tacrolimus in the acute postoperative period) or by facilitating opportunistic infections in the months after transplantation. Other neurologic syndromes such as akinetic mutism and osmotic demyelination may also occur. While much of this neurologic dysfunction may be reversible if related to metabolic factors or drug toxicity (and the etiology is recognized and reversed), cases of multifocal cerebral infarction, hemorrhage, or infection may have poor outcomes. As transplant patients survive longer, delayed infections (such as progressive multifocal leukoencephalopathy) and post-transplant malignancies are increasingly reported.

Neurotoxicity including posterior reversible encephalopathy syndrome after initiation of calcineurin inhibitors in transplanted methylmalonic acidemia patients: Two case reports and review of the literature

“…We recommend considering CNI‐induced neurotoxicity in all transplanted MMA patients presenting with new onset of seizures after transplantation. In CNI‐induced seizures more recently developed anticonvulsants should be used and no valproic acid …”

“…CNI-induced neurotoxicity frequently presents with seizures, both in transplanted MMA patients (5/7 with CNI-induced neurotoxicity and 3/3 with PRES and in the majority of non-MMA patients with CNI-induced PRES). 15,19,28 We recommend considering CNI-induced neurotoxicity in all transplanted MMA patients presenting with new onset of seizures after transplantation. In CNI-induced seizures more recently developed anticonvulsants should be used and no valproic acid.…”

“…These neurological complications can be caused by a variety of factors including immunosuppressive medication (especially calcineurin inhibitors [CNI], such as tacrolimus and cyclosporine) . CNI‐induced neurotoxicity in non‐MMA organ transplanted patients can present with a variety of symptoms such as confusion, tremor, seizures, cerebral hemorrhage, ischemic stroke, and posterior reversible encephalopathy syndrome (PRES) . In CNI‐induced PRES, the brain magnetic resonance imaging (MRI)‐scan typically shows bilateral areas of vasogenic edema, which may be located in the cortex and/or subcortical white matter of brain areas; supplied by posterior circulation.…”

“…However, new neurological complications are also a disturbing and relatively common phenomena in non-MMA patients after organ transplantation (occurring in 15%-40% of patients). [15][16][17] These neurological complications can be caused by a variety of factors including immunosuppressive medication (especially calcineurin inhibitors [CNI], such as tacrolimus and cyclosporine). 17 CNIinduced neurotoxicity in non-MMA organ transplanted patients can present with a variety of symptoms such as confusion, tremor, seizures, cerebral hemorrhage, ischemic stroke, and posterior reversible encephalopathy syndrome (PRES).…”

“…17 CNIinduced neurotoxicity in non-MMA organ transplanted patients can present with a variety of symptoms such as confusion, tremor, seizures, cerebral hemorrhage, ischemic stroke, and posterior reversible encephalopathy syndrome (PRES). 15,[18][19][20] In CNI-induced PRES, the brain magnetic resonance imaging (MRI)-scan typically shows bilateral areas of vasogenic edema, which may be located in the cortex and/or subcortical white matter of brain areas; supplied by posterior circulation. However, an atypical distribution pattern is not infrequently observed, for example, involving the basal ganglia and/or the brain stem, 20 with or without atypical imaging findings (contrast enhancement, hemorrhage or restricted diffusion).…”