Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A Multidisciplinary Perspective.

The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.

Delayed diagnosis of posterior reversible encephalopathy syndrome (PRES) in a parturient with preeclampsia after inadvertent dural puncture.

Posterior reversible encephalopathy syndrome is a rare complication generally associated with headache and acute changes in blood pressure. We present a case of posterior reversible encephalopathy syndrome where diagnosis was delayed because the patient also had preeclampsia and an inadvertent dural puncture, both associated with headache. The clinical challenge and the need for prompt diagnosis and treatment are emphasized.

Tacrolimus-associated mutism after orthotopic liver transplantation.

BACKGROUND: Mutism/speech apraxia has been well documented as a toxic effect of cyclosporine after liver transplantation but has been reported only rarely with tacrolimus. Brain imaging with magnetic resonance or computed tomography has failed to demonstrate abnormalities in affected patients. METHODS: We present the first example of an acute onset of loss of speech associated with a sudden elevation of serum tacrolimus level after successful orthotopic liver transplantation. We also describe the positron emission tomography (PET) scan of this patient's brain. RESULTS: PET scan imaging of the brain was abnormal, demonstrating decreased metabolism in the posterior temporo-parieto-occipital regions. Statistical probability mapping revealed additional areas of hypometabolism in the cingulate gyrus. CONCLUSIONS: PET scan revealed abnormalities of the brain in a patient with tacrolimus-induced mutism. The cingulate gyrus may play a role in the mutism/speech apraxia syndrome seen with cyclosporine/tacrolimus neurotoxicity.

Central nervous system complications in liver transplant recipients--incidence, timing, and long-term follow-up.

BACKGROUND: Neurological impairment is a major source of morbidity and mortality following orthotopic liver transplantation (OLT). We reviewed our experience with neurologic complications among our first 463 consecutive adult OLT recipients. METHODS: Between September 1988 and October 1993, 463 adult patients underwent OLT. Data on incidence, time of onset, and outcome of central nervous system (CNS) complications was obtained from patient charts, including autopsy results when available. CNS complications were classified by clinical presentation and by etiology. RESULTS: 93 patients (20.1%) had CNS complications following OLT. Encephalopathy (11.8%) and seizure (8.2%) were the leading complications. The incidence of immunosuppressive drug-related complications was 5.6%; coma, 1.7%; cerebral hemorrhage, 1.5%; central pontine myelinolysis (CPM), 1.2%; stroke, 0.6%; and primary CNS lymphoma, 0.2%. Most CNS events (80%) were encountered in the first month after OLT. In the majority of cases, encephalopathy (70%) and seizure (50%) presented in the first 2 wk. Although most CNS infections occurred early, 2 patients developed tuberculous meningitis more than 1 yr post-OLT. In 12 patients, death was directly related to CNS complications (2.6%). CONCLUSIONS: Most CNS complications occur early following OLT but may be seen even after 1 yr. Patients may survive serious neurologic events, such as cerebral hemorrhage, CPM, and meningitis.

Cyclosporine levels in cerebrospinal fluid after liver transplantation.

BACKGROUND: The mechanisms underlying cyclosporine neurotoxicity remain undefined. Particularly, whether cyclosporine (CyA) enters cerebrospinal fluid (CSF) or brain tissue is disputed. METHODS: We analyzed CSF from 17 lumbar punctures performed in 14 liver recipients receiving CyA and experiencing neurological complications, fever of unknown origin, seizures, or altered mental status. Whole blood samples were assayed for CyA and its metabolites. Liver function tests, serum electrolytes, and cholesterol were also analyzed. RESULTS: Four patients had cyclosporine metabolites in the CSF. These patients had acute renal insufficiency and significantly higher blood urea nitrogen (BUN) and total and direct bilirubin and alkaline phosphatase levels than patients without CyA metabolites in CSF (P < 0.05). Whole blood levels of CyA parent drug were similar between groups. Levels of CyA metabolites in the blood were significantly higher in patients with metabolites in the CSF. CyA parent drug was undetectable in CSF in both groups. CONCLUSIONS: This is the first prospective report of CyA metabolites in the CSF of transplant recipients. Acute renal insufficiency and high bilirubin levels may be associated with entry of CyA metabolites into the CSF.

Anticardiolipin antibody-associated stroke after liver transplantation.

Stroke is uncommon after orthotopic liver transplantation. We offer the first report, to our knowledge, of two posttransplant patients with stroke associated with elevated anticardiolipin antibodies, and we discuss their management, including the use of immunosuppression and antithrombotic therapy. We suggest that anticoagulation is the treatment of choice for such patients.

Reversible cerebral perfusion abnormalities associated with cyclosporine therapy in orthotopic liver transplantation.

A 60-yr-old woman experienced several episodes of generalized seizures following 2 wk of immunosuppressive therapy with cyclosporine for orthotopic liver transplantation. CT showed low density in the white matter of the parieto-occipital lobes. A 99mTc-HMPAO brain SPECT showed diminished perfusion in the parieto-occipital cortex bilaterally. Although the cyclosporine was discontinued, the patient's neurologic status initially worsened and then improved over the next several days. Repeat perfusion brain SPECT showed resolution of most of the perfusion abnormalities, while repeat CT showed persistent white matter changes in the parieto-occipital lobes. We report the presence of reversible cortical perfusion abnormalities in conjunction with cyclosporine therapy. The findings suggest that perfusion brain SPECT may be a sensitive monitor of cyclosporine-induced neurotoxicity.

Progressive multifocal leukoencephalopathy after orthotopic liver transplantation.

Six weeks after liver transplantation, a 51-year-old man developed a slowly progressive hemiparesis with deteriorating mental status and seizures. Successive computed tomography (CT) scans of the brain revealed unilateral nonenhancing white matter lucencies that gradually coalesced and progressed to both hemispheres. Brain biopsy results were consistent with progressive multifocal leukoencephalopathy (PML). We believe this is the first antemortem description of PML after liver transplantation. Herein, we describe the case and review the literature on PML after solid organ transplantation. Early recognition of this central nervous system disease may be important with new advances in therapy of this viral infection of the immunocompromised patient.

Loss of speech after orthotopic liver transplantation.

Alteration of speech is a rare but distressing complication of orthotopic liver transplantation (OLT). We describe a characteristic speech disorder identified in a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525 adults underwent OLT. For all recipients with neurologic complications, we reviewed clinical findings, imaging and electrophysiologic test results, and perioperative laboratory data. Five patients (ages 23-52; UNOS status 3-4) exhibited a characteristic pattern of stuttering dysarthria, leading to complete loss of speech production, occasionally with elements of aphasia. In four of the five patients, right-sided focal seizures were subsequently noted. All cases presented within the first 10 postoperative days and improved with 1 month of cessation of cyclosporin (CyA), although halting, monotonous speech was evident to some degree in all five for up to 1 year. There was no correlation between onset of symptoms and CyA levels. None of the patients has clinical or radiologic findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and Spect scan results were consistent with dysfunction in the left frontotemporoparietal regions of the brain. A characteristic speech disorder, which may be described as cortical dysarthria or speech apraxia, occurs in approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome and temporary cessation of CyA therapy may favorable affect the course.

Neurologic complications of orthotopic liver transplantation.

Neurologic complications are frequent after liver transplantation and are the cause of significant morbidity and mortality. A substantial proportion of the neurologic complications encountered after transplant is iatrogenic--the consequence of the harsh therapeutic interventions required to maintain function of the transplanted liver. The preoperative condition of the patient is also a major determinant of the incidence and impact of neurologic complications, as is the occurrence of poor early graft function or of repeated rejection episodes that require augmented immunosuppression. By recognizing the early signs of drug-related neurotoxicity, it is often possible to preempt the development of more severe trouble. Careful perioperative fluid management, specifically related to sodium and glucose levels, may reduce the risk of CPM. As effective treatment modalities have emerged, an aggressive approach to the diagnosis of central nervous system infection has assumed increased importance. With persistent attention to the details of basic patient care as well as to the specific neurologic diagnosis, and with a commitment to intensive rehabilitation therapy, the large majority of patients who suffer neurologic complications after transplant can ultimately return to a productive life.

Ascending back pain and headache during attempted epidural placement.

A 30-year-old parturient requested epidural analgesia during labor. Immediately after the epidural space was presumably identified using the loss-of-resistance-to-air technique, she reported severe back pain, followed by neck pain, which progressed to severe unrelenting headache. An emergency computerized tomographic (CT) scan performed during labor showed air in the intracranial subarachnoid space.

[Quasi-normal cerebrospinal fluid in patients with acquired immunodeficiency syndrome and cryptococcal meningitis]. / Liquide céphalo-rachidien quasi-normal chez des patients atteints du syndrome d'immunodéficience acquise et d'une méningite à cryptocoque.

We report eight patients with cryptococcal meningitis and a cerebrospinal fluid characterized by few or no white blood cells and chemistries that may be near normal. In four of these patients, only testing for cryptococcal antigen allowed the initial diagnosis. Seven of the patients had a certain diagnosis of AIDS. Six have died. Autopsies performed in two cases indicated a poor meningeal inflammatory response. Contrary to the findings in most immunodeficient patients, in AIDS cryptococcal meningitis may present with few cellular or biochemical abnormalities in the cerebrospinal fluid. In AIDS patients presenting with headache and fever or change in mental status, examination of the cerebrospinal fluid should not be limited to routine studies.