REYE (RAY'S) SYNDROME: A PROBLEM EVERYONE SHOULD REMEMBER.

Reye syndrome is a rare but a very dangerous emergency that children and teenagers suffer. This threatening condition occurs during the treatment of fever in the clinical course of viral diseases with drugs containing acetylsalicylic acid and other salicylates. The high mortality rate from this disease is associated with the development of a rapidly progressing toxic encephalopathy and hepatic insufficiency. The etiology and pathogenesis of the Reye syndrome, despite the large number of investigations, is not clear enough. Today, special attention is paid to the development of so-called Reye-like syndromes in the context of congenital metabolic defects, although cases of the true Reye syndrome occur quite often. In spite of the long discussion among scientists, the effect of acetylsalicylic acid is an important factor of development of this pathological syndrome. Taking this fact into consideration, the use of acetylsalicylic acid by children, especially in case of colds, should be strictly controlled by a doctor and parents should be informed about possible complications, especially the development of the Reye syndrome. This issue is very urgent in countries with non-prescription antipyretics realization and a high percentage of self-treatment among patients.

Hyponatremic seizures and Reye syndrome.

The review questions that are featured in each of the issues of the JEN are based upon the Emergency Nursing Core Curriculum and other pertinent resources to emergency nursing practice, pediatric and adult. These questions offer emergency nurses an opportunity to test their knowledge about their practice. These questions appear both in print and online.

Management of acute mitochondriopathy and encephalopathy syndrome in pediatric intensive care unite: a new clinical entity.

Acute mitochondriopathy and encephalopathy syndrome (AMES) is described differently by different authors in the literature. As a new clinical entity, we aimed to present the clinical signs and symptoms, diagnosis and treatment algorithm of our patients with AMES. 56 patients aged between 2 months and 18 years who were followed up in pediatric intensive care units of Konya Training and Research Hospital and Selcuk University Medical Faculty Hospital, between January 2010 and June 2017 were included. Patients' data were obtained retrospectively from the intensive care unit patient files. 34 (60.7%) of the patients were male and 22 (39.3%) were female. The median age of our patients was 10.0 months. At the time of admission, 42 (75%) of the patients had fever, 35 (62.5%) vomiting, 27 (48.2%) abnormal behaviour and agitation and 28 (50%) convulsion. The etiological classification of patients with AMES was divided into four groups as infection, metabolic disorder, toxic, and hypoxic-ischemic. 39 (69.6%) patients were found to have infection, 10 (17.9%) patients hypoxia, 7 (12.5%) patients metabolic disorders. AMES occurs rarely, but should be kept in mind in the differential diagnosis of patients with any encephalopathy of unknown origin especially in those with a history of ingestion of drugs, previous viral infection and vomiting. Early recognition and treatment is imperative to reduce morbidity and mortality in children with AMES.

Reye's and Reye's-like syndromes.

The review reports various questions about Reye's syndrome and Reye's-like syndromes. Although there is a significant decrease in the classic Reye's syndrome cases, because of the reduced employment of salicylates in children (salicylate seems to be the most important inducing factor of the syndrome in paediatric subjects affected by viral infection), the problem is still of interest considering the presence of different Reye's-like forms. All these pathological situations are associated with various aetiologic or predisposing causes that are examined in the text. Particular attention is placed on metabolic disorders, especially of fatty acid metabolism, and also of one amino acid. In fact, a latent form can also be the basis of possible biochemical disturbances induced by various exogenous factors such as viral infections, particularly of the respiratory tract (more rarely of bacterial aetiology), or produced by microbial toxins, or by chemical substances, including some therapeutic drugs. A full discussion of biochemical mechanisms of salicylate-induced Reye's syndrome is reported. Finally a possible diagnostic differentiation from classic Reye's syndrome and Reye's-like syndromes plus therapeutic prospects are briefly examined.

Reye's syndrome: clinical progression and evaluation of therapy.

The hospital course and therapy of 369 patients with Reye's syndrome were evaluated. Eighty-three percent of patients had deepening coma during hospitalization. Stage of coma on admission, evidence of increased intracranial pressure, and blood ammonia levels greater than 300 microgram/100 ml were all significantly associated with increasing mortality. Among survivors of Reye's syndrome, 30% of those who developed either decerebrate posturing or seizures during hospitalization had serious neurologic sequelae upon discharge. When analyzed by (1) stage of coma during admission (2) progression of coma during hospitalization, (3) degree of blood ammonia level elevation, and (4) presence of increased intracranial pressuring, no significant differences were noted between patients receiving intensive supportive care and those receiving exchange transfusions and/or peritoneal dialysis.

Hypercatecholaminemia in Reye's syndrome.

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Urea nitrogen excretion in critically ill children.

Urinary urea nitrogen (UUN) excretion as an index of both total nitrogen excretion and protein catabolism was assayed in 32 children (aged 2 months to 15 years, median 6 years) (50% mechanically ventilated) during an intensive care unit course of one to ten days (median three days). The daily UUN excretion was 4.38 +/- 2.22 gm/sq m (171 +/- 89 mg/kg) (N = 121 patient days). The average daily UUN excretion (N = 32 children) was well described by a linear regression equation for square meters of body surface area (BSA) (milligrams of UUN = 4,421.5 x BSA; r2 = .903). This linear relationship permitted the valid comparison of both individuals and subgroups despite wide age differences. Excretion data in the mechanically ventilated vs the spontaneously breathing children, and in four diagnostic subgroups (Reye syndrome, seven; sepsis, six; elective surgery, seven; and miscellaneous, 12) were evenly distributed about the regression line for body surface area. Variability in average daily UUN excretion was on individual basis, and was independent of diagnostic or therapeutic subgroup.

In vivo proton magnetic resonance spectroscopy in a case of Reye's syndrome.

A case of a 14-year-old boy with Reye's syndrome (RS) and complete neurologic recovery is presented. 1H magnetic resonance spectroscopy was performed on days 1 (admission to ICU), 8 and 62: During the acute phase of RS substantial cerebral metabolic imbalances were observed and their normalization monitored. The spectra from day 1 featured extremely high glutamine content (approximately 18 mmol/kg excess) and low concentrations of choline compounds pounds (approximately 1 mmol/kg deficit). Also some excess lactate was present. The subsequent spectra demonstrated the return to an almost normal brain metabolite profile.

Management of severe cerebral edema in the metabolic encephalopathy of Reye-Johnson syndrome.

Fifteen critically ill children with the diagnosis of Reye-Johnson syndrome were treated with techniques developed to maintain adequate cerebral perfusion pressure and levels of circulating blood glucose. One child died, three sustained neurological deficit, and nine children (70%) recovered without significant neurological dysfunction. The technique developed during the period these children were treated, the indications for their use, and factors that can interfere with maintaining adequate cerebral perfusion in patients with increased intracranial pressure from metabolic encephalopathy are described. The results suggest that neurological damage in this syndrome results from neuronal injury secondary to inadequate cerebral perfusion and/or hypoglycemia, and that neurological dysfunction like hepatic dysfunction should produce minimal mortality and morbidity if cerebral perfusion and adequate levels of circulating blood glucose are sustained during the period of increased intracranial pressure and liver failure.

Total blood washout and exchange. A valuable tool in acute hepatic coma and Reye's syndrome.

Total body washout (TBW) was accomplished thirteen times in twelve patients, with response in five and survival in three. TBW can be done without apparent harm to patients and is less laborious and more rapidly effective than repeated exchange transfusion. Early application of TBW in stage III to stage IV hepatic coma may increase survival and possibly prevent progression of metabolic derangements. Patients with stage III to IV Reye's syndrome probably should have TBW promptly, without time-consuming attempts at exchange transfusion. Based on our experience, further application of TBW is warranted in coma due to acute hepatic failure and stage III to IV Reye's syndrome.

Reye syndrome.

Reye syndrome has emerged as the quintessential example of an acute metabolic encephalopathy. The clinical presentation is quite stereotyped in most instances permitting rapid, accurate diagnosis and early therapeutic intervention. Intoxications and certain inborn metabolic errors may mimic Reye syndrome. All patients with a recurrent episode should be investigated thoroughly for evidence of a metabolic disorder associated with an enzyme deficiency. Notable in this regard are inborn errors affecting organic acid, ammonia, and carbohydrate metabolism. The mitochondrial disturbance in Reye syndrome is well documented but the pathophysiologic sequence linking the antecedent viral illness to the mitochondrial injury remains obscure. Recent identification of a spontaneous Reye-like illness in mice that is associated with a coronavirus infection may provide an opportunity to investigate this initial phase of the pathophysiologic sequence. The primary cerebral insult presumably derives from insufficient substrate availability and results in massive cytotoxic cerebral edema. Treatment revolves around the continuous infusion of hypertonic glucose and intermittent infusion of hypertonic mannitol. Management is designed to attenuate or avoid the various compounding metabolic insults during this critical period when the child is metabolically crippled. In 1963, the disorder was considered to be rare and almost irreversibly fatal. Today, the disorder is recognized to be more common, and the outcome is very satisfactory in 85 to 90 per cent of the cases. The role of aspirin remains very controversial. A number of studies suggest an association between this potential mitochondrial toxin and Reye syndrome, but a causal relationship has not been established. Until better understood, it seems advisable to avoid use of aspirin in children exhibiting symptoms suggestive of Reye syndrome.

Management of Reye's syndrome.

Reye's syndrome is a potentially devastating neurologic illness seen predominantly in children following a viral prodrome. The cause is unknown. The clinical history and laboratory presentation are stereotypical and easy to recognize if the clinician considers the diagnosis. Neurologic dysfunction is characterized by lethargy, obtundation, persistent vomiting, agitated delirium, and coma. Death is secondary to severe cerebral swelling with elevation of intracranial pressure. Although no specific therapy has been clearly demonstrated to be superior in terms of outcome, most clinicians have adopted a management scheme aimed at lowering and controlling the elevated ICP. We have described the management protocol in use at the Children's Hospital of Philadelphia. The protocol is summarized in the Appendix for the convenience of the reader.

Effects of therapeutic agents in a rabbit model of Reye syndrome.

Six potential therapeutic agents were evaluated in an experimental model simulating Reye syndrome produced by infusion of the short-chain fatty acid, sodium octanoate, into rabbits. Administration of carnitine, dexamethasone, or fatty acid-free albumin resulted in prolongation of survival, less rise in intracranial pressure, and amelioration of some of the metabolic abnormalities found typically during octanoate infusion. Treatment with pentobarbital or dimethyl sulfoxide prevented intracranial pressure elevations but had no protective effect on survival. Hypertonic glucose administration produced no improvement in any of the parameters studied.

Reye syndrome: a predictably curable disease.

Seventeen years after the initial description of this syndrome of hepatic failure and encephalopathy, the etiology and pathophysiology are still not well defined. Clinical staging of the disease proposed by Lovejoy and colleagues is helpful and is recommended as a standard to be followed by referring physicians and hospital-based pediatricians and intensivists. A new classification based on the status of intracranial pressure and unrelated to clinical, laboratory, or EEG staging is presented.

Monitoring and control of intracranial pressure in non-traumatic encephalopathies.

Fifteen patients with non-traumatic encephalopathies underwent continuous monitoring of intracranial pressure. These included 11 children with Reye's syndrome, two with viral encephalitis, one with mushroom poisoning, and one with hypoxia from drowning. Elevated intracranial pressure was treated with decadron, hyperventilation, hyperosmolar agents and in some cases hypothermia and barbiturates. The results are discussed.

Monoclonal antibody therapy in the treatment of Reye's syndrome.

A role for lipopolysaccharides (endotoxins, LPS) in 7 the pathogenesis of Reye's syndrome (RS) has previously been suggested. Impairment of hepatic LPS clearance can lead to systemic endotoxemia as previous studies by this and other laboratories have suggested for several hepatic disorders including RS. Systemic LPS may mediate many of the clinical findings associated with RS by eliciting monokines such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interleukin-8. Monoclonal antibody therapy directed at LPS, and monokines may represent a novel approach to the treatment of RS.

Reye's syndrome.

Although most cases of Reye's syndrome that were initially reported were fatal, the overall mortality is now 20 to 30 per cent, with an even lower rate in some series. Improvement is due to both increased awareness of this disease and advances in care for the critically ill child. A good outcome depends on recognition of the early manifestations of the syndrome and appropriate initial therapy based on the stage of the disease.

[Clinical picture of Reye's syndrome in an adult]. / Quadro clinico di sindrome di Reye in un adulto.

The case of a young man of 20 who, after aspecific prodromic symptomatology of viral type, presented a clinical picture characterised by encephalitis and hepatitis classifiable in Reye's syndrome is reported. Bioenzymatic data and therapeutic outlook are discussed.