Neurologic Complications of Organ Transplantation Treatment & Management

Once the diagnosis is made, medical treatment of neurologic complications in transplant recipients is not significantly different from that in nontransplant patients. Nevertheless, complex drug interactions that may potentially compromise immunosuppression and allograft function must be considered.

• Encephalopathy: Impairments of consciousness of variable etiology and severity, from mild confusion to coma, are not uncommon in transplant recipients. Establishing the cause determines further treatment, and delirious patients may also need symptomatic treatment (neuroleptics). In patients with toxic-metabolic encephalopathies, treatment is directed towards correcting the underlying cause while providing medical support (eg, respiratory support, parenteral feeding). In patients with hyponatremia, gradual correction is recommended.
• Seizure

  • The underlying etiology of seizures and overall medical condition (including type of allograft and comorbidities) determine which antiepileptic drugs (AEDs) are used for treatment. Symptomatic seizures resulting from transient toxic and metabolic disturbances are treated by correcting the metabolic disturbance.
  • The most commonly used AED in transplant recipients is phenytoin because it is effective and simple to administer. Benzodiazepines (eg, lorazepam, diazepam) are useful in the acute management of seizures, whereas propofol is a third-line agent used for treatment of refractory status epilepticus. Phenobarbital is rarely used because of activation of liver enzymes, sedation, and long half-life, but it may be helpful in individual patients. Other medications used for treatment of refractory status epilepticus include midazolam and pentobarbital.
  • Levetiracetam should be considered for acute and maintenance treatment of seizures given the availability of an intravenous form and relative lack of drug-drug interactions. Because it is cleared by the kidney, it can be used in patients with liver failure. Levetiracetam should not be considered a first-line treatment for refractory status epilepticus. Adverse effects include sedation and encephalopathy.
  • Valproic acid may be helpful in patients allergic to phenytoin or if phenytoin cannot be used because of drug interactions. Its use is avoided in children younger than 2 years and in liver transplant recipients because of potential hepatotoxicity. Use of carbamazepine and oxcarbazepine is limited by the lack of a parenteral form.
  • Newer AEDs are mostly used as adjunctive agents, and the lack of significant drug interactions of topiramate, pregabalin and gabapentin makes them very attractive in transplant patients.
• CNS infections: CNS infections carry high risk of morbidity and mortality. Because presenting signs and symptoms may be quite subtle in transplant recipients who are immunosuppressed, CNS infection should almost always be considered in the differential diagnosis. Depending on the clinical setting, therapy may be initiated with broad coverage (ie, antibiotic, antifungal, antiviral) or may be more focused. Delaying treatment may have catastrophic consequences.
• Stroke and intracranial hemorrhage

  • The treatment of ischemic stroke in transplant recipients depends on the etiology and type of stroke (eg, cardioembolic, thrombotic, CNS infection, hypercoagulable state) as in nontransplant patients. Long-term control of cerebrovascular risk factors (eg, cholesterol, glucose control, hypertension, tobacco use) is needed as in nontransplant patients, particularly as improved protocols enable long-term survival. Some immunosuppressive medications (ie, sirolimus, cyclosporin) may worsen or trigger hyperlipidemia and hypertension.
  • Intracranial hemorrhage may be difficult to treat in transplant recipients, particularly if it is associated with coagulopathy, thrombocytopenia, or CNS infection.
  • Replacement of platelets and clotting factors (fresh frozen plasma) is needed in patients with thrombocytopenia and coagulopathy.
• Neuromuscular disorders: Treatment of neuromuscular complications of transplantation is identical to that in nontransplant patients. Most common neuromuscular disorders in transplant recipients are perioperative neuropathies and critical illness myopathy/polyneuropathy (CIM/CIP). Treatment of patients with perioperative neuropathies and CIM/CIP is supportive with early initiation of physical therapy. Cautious use of paralytic agents and steroids in intensive care settings may decrease the occurrence of CIM. Patients with refractory myasthenia associated with chronic GVHD may benefit from rituximab.

• Surgical removal of a cerebral hematoma in the acute stage, either by evacuation or aspiration, may be lifesaving.
• Brain biopsy obtained by open or stereotactic technique is helpful in the evaluation of cranial masses of unknown origin, particularly if PTLD or brain tumors are suspected.
• The decision to proceed with aspiration or open removal of a brain (or spinal cord) abscess is guided by the location, clinical course, and the degree of mass effect exerted by the abscess on the surrounding tissue. Stereotactic aspiration can be performed with deep abscesses.
• Decompressive surgery is an emergency treatment of rapidly evolving hydrocephalus that is not responding to medical measures (ie, hyperventilation, mannitol).
• Intraventricular placement of an Ommaya reservoir permits intrathecal treatment of fungal CNS infection.

A multidisciplinary approach is essential to the effective care of a transplant recipient. The transplant team has a central role in determining the level of immunosuppression. Various consultants play active roles in the care of these patients.

• A neurologist is usually a consultant in the management of transplant patients, but may also admit the patient to neurology service.
• Transplant team members have a central role in the treatment of transplant recipients. They coordinate with other teams and determine the required level of immunosuppression.
• A critical care medicine specialist is particularly important in the early postoperative course.
• An infectious disease specialist is invaluable in helping to evaluate possible opportunistic systemic and CNS infections.
• Consulting a physical therapist is important because early initiation of physical therapy may accelerate recovery of transplant recipients.
• Other medical and surgical specialists (including nephrologists, pulmonologists, cardiologists, neurosurgeons, and others) are also actively involved in the care of transplant recipients, depending on the type of allograft, comorbidities, and ongoing medical problems.

Following transplantation, various dietary products may interfere with pharmacokinetics of immunosuppressive and other medications (eg, grapefruit juice).

• Certain foods may increase risk of infection such as raw milk, soft cheeses, and hot dogs (Listeria monocytogenes).
• Sodium restriction (2 g/d) may be helpful in management of cyclosporine-related hypertension.
• Rapamycin and, to a lesser extent, cyclosporine are associated with hypercholesterolemia. Conversion from cyclosporine to tacrolimus may be helpful.
• Use of statins in combination with cyclosporine may lead to rhabdomyolysis.

No specific activity restrictions are necessary for patients with neurologic complications of transplantation.