Neuropathology of Pediatric Liver Transplantation

Hall, Walter A.; Martinez, Armando E. Rodriguez

doi:10.1159/000120482

Cited by 22 publications

(12 citation statements)

References 8 publications

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“…McCarron and Prayson found, among 16 patients who died after undergoing orthotopic liver transplant, 4 patients with type II astrocytes. 13 In similar circumstances Blanco et al 14 found type II astrocytes in 30% of the cases, and Hall and Martinez 15 found them in 69% of pediatric cases status post Figure 1. Hematoxylin-eosin-stained section of basal ganglia illustrating type II astrocyte (arrows) with oligodendrocytes (arrowhead).…”

Section: Discussionmentioning

confidence: 82%

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

Agarwal

Mais

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Hepatic encephalopathy (HE) is associated with presence of type II astrocytes in the brain on the basis of observations made in single uncontrolled cases. This finding was subsequently demonstrated by in vitro studies with replication of microenvironment of HE by increase in ammonia levels. However, no human studies have been done correlating HE with type II astrocytes.Objective.-To determine the sensitivity and specificity of type II astrocytes in HE.Design.-This is a retrospective cohort study in which cases and controls were included. A database search was conducted to identify potential cases of hepatic encephalopathy during a 3-year period, as well as concomitant cases with altered mental status from other causes, liver disease, both, and neither. The presence of HE was determined according to standard clinical criteria, and a coronal section of basal ganglia was selected for examination from each case. Type II astrocytes were enumerated over 20 random high-power fields (HPFs).Results.-Twenty-one patients with HE were identified, with 35 patient controls (18 females, 38 males). Among the patients with HE there was a mean of 19.8 type II astrocytes in 20 HPFs. Patients with altered mental status without HE had an average of 7.2 type II astrocytes per 20 HPFs, and for those without altered mental status, the average was 2.8. For patients with hepatic insufficiency without HE, the average was 11, while for patients with normal hepatic function, the average was 4.1. Overall, for those without HE, the average was 5.4 type II astrocytes per 20 HPFs.Conclusions.-At a cutoff of 5 or more type II astrocytes per 20 HPFs, sensitivity for HE was 85.7% and specificity was 68.6%. Alzheimer type II astrocytes were present in all cases of HE but were also present in a wide variety of patients without HE.H epatic encephalopathy (HE) is a neuropsychiatric disorder that arises in patients with severe hepatic dysfunction and in patients with portosystemic shunts. It manifests as clinical delirium characterized by behavioral changes and cognitive impairment. 1 In severity, manifestations vary from irritability to delirium, stupor, and coma. In a study by Fichet et al, 2 hepatic encephalopathy was associated with a mortality of 54% at 1 year.A distinct cell type was first noted by von Hösslin and Alzheimer in 1912 and came to be known as the Alzheimer type II astrocyte, the histopathologic hallmark of HE. 3,4 Hyperammonemia results when, because blood bypasses the liver or passes through dysfunctional liver, ammonia is insufficiently converted to urea. [5][6][7][8] This is thought to be the cause of neurologic dysfunction in HE. Furthermore, experimental evidence demonstrates that the distinctive morphologic features of type II astrocytes can be induced by ammonia in vitro, and observational studies confirm that type II astrocytes are observed in animals and human patients with HE. 9-11 It is thought that these changes reflect induction of neuroprotective metabolic pathways in astrocytes in the hyperammonemic environment...

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Section: Discussionmentioning

confidence: 82%

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

Agarwal

Mais

2019

Archives of Pathology &Amp; Laboratory Medicine

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“…Neurologic complications are the most important causes of morbidity and mortality in liver transplant recipients [1,2,3,4,5], with seizures being one of the leading complications, having a frequency between 2.8 and 42% [1, 3,5,6,7,8]. Etiologies of seizures include infection, stroke, central pontine myelinolysis, and acute metabolic insults induced by immunosuppressive therapy [1,5,6,7,8,9,10]. It is often difficult to establish the precise causes of seizures in patients who have undergone OLT, however, because multiple potential causes may be present.…”

Section: Introductionmentioning

confidence: 99%

New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

et al. 2004

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Purpose: To identify the probable etiologies and characteristics of new-onset seizures after orthotopic liver transplantation (OLT) and to assess their clinical implications and prognosis. Methods: We retrospectively analyzed the clinical, electrophysiologic and laboratory data of 17 patients with new-onset seizures after OLT among 367 adult and pediatric patients who underwent OLT between 1999 and 2001. Results: A suspected etiology of seizures was identified in most patients, including 6 (35.2%) with neurotoxicity due to immunosuppressive therapy, 4 (23.5%) with cerebrovascular disease, 3 (17.6%) with severe metabolic derangement by sepsis or rejection, and 1 each (5.8%) with hyperglycemia and brain edema due to fulminant hepatic failure. Causative factors could not be identified in 2 patients (11.8%). Seizures recurred in 15 patients (88.2%), with 9 occurring on the same day as the original seizure. Attacks caused by neurotoxicity tended to have an earlier onset, within 1 week in 4 of 6 patients, than those caused by cerebrovascular disease and sepsis/rejection, but this was not statistically significant. A total of 21 EEGs were performed in 13 patients. Eleven patients had abnormal EEG findings, of whom 4 (30.7%) showed epileptiform discharges, but the outcome of patients with epileptiform activity did not differ statistically from that of patients without such discharges (p > 0.6). The incidence of poor outcome (death or persistent vegetative state) in the group with seizures was almost 10 times higher than in the group without seizures (52.9 vs. 5.7%, p < 0.001). The prognosis of patients with seizures due to cerebrovascular disease and severe metabolic derangement by sepsis/rejection was poorer than that of patients with seizures caused by the neurotoxicity of immunosuppressive drugs (p < 0.02), suggesting that the underlying cause of seizures is important in determining prognosis. Of 8 patients who survived, 1 was lost to follow-up. The long-term outcome of seizures in surviving patients was excellent, with all survivors available for follow-up being seizure-free for a mean follow-up of 42.5 months (range, 16–58 months). Conclusion: New-onset seizures after OLT may herald fatal outcome, especially in patients with cerebrovascular disease or sepsis. The prognosis of seizures in survivors is excellent, and long-term antiepileptic drugs are not required in most cases.

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“…To the best of our knowledge, 10 cases of CPM after pediatric LT were reported worldwide between 1989 and 2012 (Table ) . Five patients died, and they were only diagnosed with CPM at autopsy.…”

Section: Discussionmentioning

confidence: 99%

“…CPM is considered to be the most serious neurological complication of OLT, with a risk of early mortality . Although most previously reported cases of CPM were diagnosed at autopsy, recent advances in MRI technology now allow for the early diagnosis of CPM . It has been reported that electrolyte imbalances, the rapid correction of the serum sodium concentration and the administration of immunosuppressive agents are associated with the development of CPM following organ transplantation .…”

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confidence: 99%

Central pontine myelinolysis following pediatric living donor liver transplantation: A case report and review of literature

Uchida

Sakamoto

Sasaki

et al. 2014

Pediatric Transplantation

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CPM is one of the most serious neurological complications that can occur after OLT and is characterized by symmetrical demyelinization in the basis pontis. The etiology of CPM remains unclear, although the rapid correction of the serum sodium and CNI concentrations may be associated with the development of CPM. With recent advances in MRI technology, early diagnosis of CPM has become possible. Here, we present the case of a five-yr-old female who developed CNI-associated CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of CPM. The patient fully recovered from the neurological deficits related to CPM following the switch from the CNI to sirolimus. We propose MRI to be promptly considered for patients with abnormal neurological findings, together with the substitution of CNI with an mTOR inhibitor as a management regimen for CNI-related CPM.

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Neuropathology of Pediatric Liver Transplantation

Cited by 22 publications

References 8 publications

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

Sensitivity and Specificity of Alzheimer Type II Astrocytes in Hepatic Encephalopathy

New-Onset Seizures after Liver Transplantation: Clinical Implications and Prognosis in Survivors

Central pontine myelinolysis following pediatric living donor liver transplantation: A case report and review of literature

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