CHAPTER 72: Postrenal Transplant: Neurological Complications

INTRODUCTION

• Renal transplants are among the most common solid organ transplants with a steady rise in their numbers, particularly over the recent years.¹ Some reports suggest that about 9 out 10 transplant recipients experience some form of neurological symptoms.² Other reports indicate that 30–60% of postrenal transplant individuals may develop some neurological complications,³ with an estimated prevalence rate of 8%.⁴ The central neurological complications may have similar clinical presentations despite their diverse etiologies. Further, these complications are frequently associated with a higher rate of morbidity and mortality. Thus, early recognition and treatment can prevent or limit life-threatening sequelae associated with these complications and optimize the clinical outcome.^4,5 In this chapter we review the central and peripheral neurological complications following renal transplant, including those related to immunosuppressants.

ENCEPHALOPATHY

• Multifactorial etiologies, including toxic-metabolic disturbances, infection, and medication-related neurotoxicity, as well as neuropsychiatric disturbances, cerebrovascular events, neoplasms such as lymphoma, progressive multifocal leukoencephalopathy (PML), posterior reversible encephalopathy syndrome (PRES), and rejection encephalopathy associated with severe rejection episodes.^5,6

COGNITIVE IMPAIRMENT

• Although specific cognitive domains improve following transplantation, some recipients experience cognitive decline, often of vascular etiology.⁷

• The prevalence of cognitive impairment is estimated to be about 15.6% among renal transplant recipients.⁷

• Older age, male gender, lower socioeconomic status, greater vascular risk factors (such as prolonged hypertension, diabetes, and obesity), and higher rate of comorbidities (such as cerebrovascular and cardiovascular diseases) at the transplant surgery are significant risk factors for cognitive decline and dementia.^7–11

• Long-term treatment with calcineurin inhibitors (CNIs) can also contribute to cognitive decline.^12,13

NEUROTOXICITY OF CNIs

• Long-term use of cyclosporine and tacrolimus, immunosuppressants commonly used in renal transplant recipients, is associated with neurotoxicity thought to be related to its ability to accelerate cerebrovascular atherosclerosis, impair cerebral mitochondrial metabolism, and accelerate neurodegeneration.¹² By contrast, other classes of immunosuppressants were shown to have a lower risk of developing dementia.¹³

• Neurological presentations can occur even with subtherapeutic levels and include:

  • Headache, dizziness, paresthesia, insomnia, tremors, and acute neuropsychiatric syndrome (such as depression, agitation, psychosis, delusions, and visual hallucinations). More serious symptoms include severe encephalopathy, progressive cognitive decline with impaired visuospatial/constructional ability, seizures, speech/gait impairments, visual disturbances, focal neurological deficits, and rarely coma.¹

  • PRES is thought to be related to vascular endothelial injury and impaired autoregulatory capacity, resulting in vasogenic edema and cerebral hypoperfusion (Figure 72-1).¹

  • Visual disturbances can be related to occipital seizures, PRES, or rarely to demyelination optic neuropathy that can be unilateral or bilateral.^12,14–19

  • Cognitive decline and central pontine myelinolysis (discussed later).

  • CNI-induced pain syndrome (CIPS); typically affects distal legs, particularly during the first year posttransplantation.¹

• Diagnosis:

  • Brain magnetic resonance imaging (MRI) may reveal cortical, subcortical, or periventricular white matter lesions related to vasogenic edema and/or leukoencephalopathy, PRES, and central pontine ...