Reye Syndrome with Severe Hyperammonemia and a Good Neurological Outcome.

BACKGROUND Reye syndrome (RS) is a rare life-threatening condition combining acute noninflammatory encephalopathy and acute liver failure with an absence of defined etiology. We present a case of fulminant RS that had a good neurological outcome. CASE REPORT A 4-year-old previously healthy boy had no history of acetylsalicylic acid (ASA) use, nor had he been diagnosed with any inborn errors of metabolism. RS was preceded by a mild viral infection, possibly caused by human bocavirus, which has not been previously implicated in RS. He presented with a combination of a very high concentration of ammonia but only mildly elevated aminotransferases and mild hypoglycemia. Computed tomography (CT) of the head additionally showed diffuse cerebral edema with tentorial herniation. The extensive metabolic evaluation did not confirm any inborn errors of metabolism to explain the etiology. We provided optimal treatment of severe hyperammonemia (>500 µmol/L) and cerebral edema, including high doses of arginine chloride, sodium benzoate, hemodialysis, mild hypothermia, and supportive care. He has been followed up for over 4 years. The patient recovered completely, with no long-term psycho-cognitive or neurological sequelae. CONCLUSIONS Although extremely rare, hyperammonemia and RS should be considered in cases of an acute encephalopathy to be treated as soon and as decisively as possible to enable a good outcome.

Atypical Reye syndrome: three cases of a problem that pediatricians should consider and remember.

INTRODUCTION: Reye syndrome is a rare acquired metabolic disorder appearing almost always during childhood. Its aetiopathogenesis, although controversial, is partially understood. The classical disease is typically anticipated by a viral infection with 3-5 days of well-being before the onset of symptoms, while the biochemical explanation of the clinical picture is a mitochondrial metabolism disorder, which leads to a metabolic failure of different tissues, especially the liver. Hypothetically, an atypical response to the preceding viral infection may cause the syndrome and host genetic factors and different exogenous agents, such as toxic substances and drugs, may play a critical role in this process. Reye syndrome occurs with vomiting, liver dysfunction and acute encephalopathy, characterized by lack of inflammatory signs, but associated with increase of intracranial pressure and brain swelling. Moreover, renal and cardiac dysfunction can occur. Metabolic acidosis is always  detected, but diagnostic criteria are not specific. Therapeutic strategies are predominantly symptomatic, in order to manage the clinical and metabolic dysfunctions. CASE REPORTS: We describe three cases of children affected by Reye syndrome with some atypical features, characterized by no intake of potentially trigger substances, transient hematological changes and dissociation between hepatic metabolic impairment, severe electroencephalographic slowdown and slightly altered neurological examination. CONCLUSIONS: The syndrome prognosis is related to the stage of the syndrome and the rapidity and the adequateness of intensive care treatments. The analysis of the patients leads to a greater awareness of the difficult diagnosis of this not well completely known syndrome.

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.

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics.

Ammonia is an important component of metabolism and is involved in many physiological processes. During normal physiology, levels of blood ammonia are between 11 and 50 µM. Elevated blood ammonia levels are associated with a variety of pathological conditions such as liver and kidney dysfunction, Reye's syndrome and a variety of inborn errors of metabolism including urea cycle disorders (UCD), organic acidaemias and hyperinsulinism/hyperammonaemia syndrome in which ammonia may reach levels in excess of 1 mM. It is highly neurotoxic and so effective measurement is critical for assessing and monitoring disease severity and treatment. Ammonia is also a potential biomarker in exercise physiology and studies of drug metabolism. Current ammonia testing is based on blood sampling, which is inconvenient and can be subject to significant analytical errors due to the quality of the sample draw, its handling and preparation for analysis. Blood ammonia is in gaseous equilibrium with the lungs. Recent research has demonstrated the potential use of breath ammonia as a non-invasive means of measuring systemic ammonia. This requires measurement of ammonia in real breath samples with associated temperature, humidity and gas characteristics at concentrations between 50 and several thousand parts per billion. This review explores the diagnostic applications of ammonia measurement and the impact that the move from blood to breath analysis could have on how these processes and diseases are studied and managed.

Diagnóstico de la encefalopatía aguda en la práctica neuropediátrica

Objetivos: Delinear los criterios para el diagnóstico de niños y adolescentes con encefalopatía aguda y las principales manifestaciones clínicas y de laboratorio de los trastornos que con mayor frecuencia motivan su asistencia a los servicios de emergencia.Desarrollo: Se delinea un algoritmo de actuación diagnóstica general ante un niño o adolescente con encefalopatía aguda. Primeramente se plantea el concepto de encefalopatía aguda. Se tuvo en cuenta que sus manifestaciones clínicas consisten fundamentalmente en trastornos de la conciencia, de las funciones mentales, de la ocurrencia de crisis epilépticas y otros signos de focalización o disfunción neurológica. En segundo lugar, ante un paciente con criterio de encefalopatía aguda, se insiste en la importancia de determinar si se tratade una encefalitis o no. Se aborda el enfoque diagnóstico ante un paciente pediátrico con encefalitis enfatizando en los principals exámenes de laboratorio y neuroimagen para diagnosticarla y su interpretación etiológica. Luego se señalan las principales encefalopatías agudas que no cumplen los criterios de encefalitis infecciosa o autoinmune y se mencionan los elementos fundamentales que las hacen sospechar.Conclusiones: La organización que se propone para el diagnóstico de encefalopatía aguda y de los trastornos que la motivan es una contribución para mejorar la atención ante esta situación grave que requiere de un manejo eficaz y rápido. Este enfoque puede ser la clave para el diagnóstico en la práctica neuropediátrica y la determinación de la conducta adecuada(AU)

Objective: To describe the necessary approaches for diagnosis of children and adolescents with acute encephalopathy, it´s main clinicalmanifestations and laboratory tests of more frequent disorders that are reason of attention in emergency services.Development: One algorithm about the general actuation for diagnosis in children and adolescents with acute encephalopathy is delineated. Initially, is established the concept of acute encephalopathy, and are considered main clinical manifestations: disorders of consciousness, mental function, and occurrence of epileptic seizures and other neurological manifestations of focalization or dysfunction. In second place, in patient with criteria of acute encephalopathy, is very important to definite if clinical manifestations are consistent with encephalitis or not. Here is presented an option for diagnosis of patient with encephalitis, emphasizing on the laboratory tests andneuroimaging for diagnosis and cause determination. After that, are mentioned the main options in diagnosis of acute encephalopathy thatdo not fulfill the criterions, neither of infectious encephalitis or immune–mediated neurologic diseases, and are mentioned fundamental elements that make to suspect them.Conclusions: The proposed organization for the diagnosis of acute encephalopathy and disorders that are motive of it, it is a contribution for to get betters the attention on this serious situation that needs an effective and fast conduct. This approach can be the key for diagnosisin child neurology practice and appropriate conduct determination(AU)

Mean platelet volume in children with Reye-like syndrome.

Reye-like syndrome (RLS) is considered to be a systemic disorder in which the cytokine storm plays a major role. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to study MPV in children with RLS. The study population consisted of 30 children with RLS and 30 healthy control subjects. White blood cell (WBC) count, aspartate transaminase (AST) and alanine transaminase (ALT) values were significantly higher and MPV values were significantly lower in patients with RLS at an early stage of illness when compared to controls. Erythrocyte sedimentation rate (ESR), C-reactive protein, AST and ALT values were significantly decreased in patients with RLS after the treatment when compared to baseline whereas MPV values were increased. MPV values were negatively correlated with ESR and WBC. In conclusion, at an early stage of RLS MPV values were lower when compared to controls.

Inicio, diagnóstico y seguimiento de un caso con deficiencia de acil-CoA deshidrogenasa de cadena muy larga / Debut, diagnosis and outcome of a case with very long chain acyl-CoA dehydrogenase deficiency

Los ácidos grasos representan el 80% de las necesidades energéticas en periodos de estrés metabólico. La betaoxidación de los ácidos grasos es catalizada por varias enzimas, como la acil-CoA deshidrogenasa-coenzima FAD, que posee 4 formas específicas según la longitud de la cadena de acil-CoA. La acil-CoA-deshidrogenasa de cadena muy larga es una de ellas. Su déficit cursa con la acumulación intramitocondrial de ésteres de acil-CoA de cadena larga, y afecta al corazón, el músculo esquelético y el hígado. Presentamos un caso iniciado a los 22 meses de edad con un síndrome Reye-like. Confirmamos un déficit de la betaoxidación de los ácidos grasos de cadena muy larga, con las mutaciones p.A232T (c.694G>A) y p.Y201C (c.602A>G) en los alelos del gen VLCAD. Describimos su evolución durante 17 años recibiendo una dieta pobre en ácidos grasos de cadena larga y suplementos con aceite MCT (AU)

Fatty acids represent 80% of energy needs during periods of stress. Beta-oxidation of fatty acids is catalyzed by some enzymes including acyl-CoA-dehydrogenase-coenzyme FAD, wich has four different ways according to the chain length of acyl-CoA. The very-long-chain-acyl-CoA-dehydrogenase is one of them. A deficiency of this enzyme produces an accumulation of long-chain-acyl-CoA-esters in mitochondrias, affecting heart, skeletal muscle and liver. We report the case of a 22-month aged child whose first symptom was a Reye-like syndrome. We confirmed that he was affected by a deficiency in the beta-oxidation of fatty acids of very long chain. He showed some mutations in the VLCAD gene alleles: p.A232T (c.694G>A) and p.Y201C (c.602A>G). We explain the evolution in the next 17 years, following a diet with very little long chain fatty acids and MCT oil supplements (AU)

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.

Case of Reye's syndrome accompanied by hemolytic anemia and cardiac injury after cytomegalovirus infection.

A 6-month-old girl with active human cytomegalovirus (HCMV) infection developed Reye's syndrome after vaccination. She suffered from uncommon complications of HCMV infection, including Coombs-negative hemolytic anemia and cardiac injury, but recovered after the appropriate treatment with prompt ganciclovir and symptomatic support. However, the patient died later as a result of a viral upper respiratory tract infection, which aggravated the primary disease. This case suggests that HCMV infection might be a causative agent of Reye's syndrome.

[21-year-old woman with Reye's syndrome after influenza]. / 21-jährige Patientin mit Reye-Syndrom nach grippalem Infekt.

HISTORY AND ADMISSION FINDINGS: A 21-year old woman was referred to the hospital because of progressively deteriorating consciousness. Initially agitation and irritability, later confusion and delirium predominated. Previously influenza with high temperature, headache and vomiting had occurred and been treated with acetylsalicylic acid for some days. Non preliminary diseases were reported. CLINICAL INVESTIGATION: Besides of the deterioration in consciousness no clinical or neurological abnormalities were found. Electroencephalography demonstrated general abnormalities of medium range. Cranial magnetic resonance imaging and liquor investigations showed no pathological findings. In laboratory tests a marked increase of transaminases and ammonia were found. The toxicological screening was normal. TREATMENT AND COURSE: A hepatic encephalopathy due to acute hepatic failure was diagnosed and a detoxication of ammonemia with lactulose was started immediately. Transjugular liver biopsy showed a marked fattening of liver tissue without serological or histological findings for a reason. Because of progressive deterioration in consciousness mechanical ventilation became necessary. Despite of a rapid decline of ammonium serum levels further neurological deterioration occurred. Cranial computed tomography showed oedema of the cerebrum with beginning cerebral occlusion. Despite immediate therapy of cerebral oedema the patient died because of secondary cerebral oedema in hepatic encephalopathy. CONCLUSION: Reye's syndrome is an acute illness characterized by hepatic encephalopathy and fatty degeneration of the liver. It often occurs after viral infections. After a viral infection that was eventually treated with acetylsalicylic acid Reye's syndrome has to be discussed after exclusion of common causes of hepatic failure.

Hyperammonemia in children: on the crossroad of different disorders.

BACKGROUND: Symptoms of hyperammonemia occur in patients irrespective of the kind of metabolic diseases. Age, metabolic and nutritional status, and decompensation factors such as infections influence clinical manifestations. Prolonged, untreated hyperammonemia leads to brain injury and intellectual disability. Treatment is directed at lowering plasma ammonia. Brain ammonium concentrations are 1.5 to 3.0 times higher than that in blood. REVIEW SUMMARY: The authors discuss the pathophysiology of the symptoms and consequences of hyperammonemia in children, focusing on the metabolic disorders leading to an increased level of ammonia. CONCLUSIONS: Ammonia toxicity has been investigated for a long time. According to the main hypotheses, the neurological alterations are connected to alterations in glutamatergic neurotransmission.

Adult Reye-like syndrome associated with serologic evidence of acute parvovirus B19 infection

Reye's syndrome is an infrequently diagnosed medical condition affecting mainly children. The etiology, epidemiology and natural history of Reye's syndrome have been cloudily written in footnotes of medical books and exotic papers since the initial description in early 1950s. We report here a case of adult Reye's syndrome associated with serologic evidence of parvovirus B19 infection.

Magnetic resonance imaging findings in Reye syndrome: case report and review of the literature.

Magnetic resonance imaging findings in Reye syndrome have been reported only infrequently. A previously well 8-year-old boy presented with repeated episodes of vomiting and abdominal pain followed by altered sensorium and tonic spasms. This occurred 5 days after upper respiratory tract infection. His laboratory data revealed elevated liver enzymes, prolonged prothrombin time, and high blood ammonia levels. Magnetic resonance imaging of the brain done on the day of admission revealed diffuse cerebral edema and signal alterations in brainstem, bilateral thalami, medial temporal lobes, parasagittal cortex, and cerebellar and subcortical white matter. Diffusion restriction was seen in thalami, midbrain, cerebellar white matter, subcortical white matter, and parasaggital cortex in the watershed territory. The patient made a full recovery. Follow-up magnetic resonance imaging after a week revealed complete resolution of all except thalamic lesions. Although diffusion restriction in thalami and midbrain has been reported previously, this is the first report indicating diffusion restriction in subcortical white matter and the parasagittal cortex.

[The Reye syndrome]. / Syndrome de Reye.

The Reye syndrome is a complex disease that remains little-known despite its severity. It can occur in children of all ages, and is often fatal, while surviving children often display neurological damage. The therapy is symptomatic and supportive. The diagnosis of Reye's syndrome is not straightforward, as the symptoms are very diverse. The causes of the disease are moreover still unclear, and, after many years of discussion and research, it can still not be proved irrefutably whether administration of acetylsalicylic acid to children suffering from viral infections is a factor in the development of Reye's syndrome.

[Reye syndrome and Reye-like syndrome].

Reye syndrome (RS) is an acute metabolic encephalopathy and hepatopathy affecting children and adolescents. Outbreaks of RS were common in United States until the early 1980s. However, after the abolition of salicylate (aspirin) therapy for infectious diseases such as influenza or varicella in patients under 18 years of age the incidence decreased. Now classical RS is rare and RS is considered a secondary mitochondrial disease. Reye-like syndrome (RLS), resulting from congenital errors of mitochondrial fatty oxidation, especially medium-chain acyl-CoA dehydrogenase deficiency, has increased due to progress in diagnostic techniques and methods after 1990. Diagnostic differentiation between RS and RLS is difficult because the end results of mitochondrial dysfunction in RS and RLS may be similar.

Adult Reye-like syndrome associated with serologic evidence of acute parvovirus B19 infection.

Reye's syndrome is an infrequently diagnosed medical condition affecting mainly children. The etiology, epidemiology and natural history of Reye's syndrome have been cloudily written in footnotes of medical books and exotic papers since the initial description in early 1950s. We report here a case of adult Reye's syndrome associated with serologic evidence of parvovirus B19 infection.

[Reye's syndrome. Description of a case focused on the patient's epileptic seizures]. / Síndrome de Reye. Descripción de un caso con especial interés en sus crisis epilépticas.

INTRODUCTION: Reye's syndrome is an acute disease characterised by encephalopathy and fatty degeneration of the liver that occurs almost exclusively in children. It can cause the death of the patient in up to a third of all cases, generally due to severe cerebral oedema. The aetiopathogenesis of this condition is uncertain and is usually preceded by a viral infection, generally from the influenza or varicella virus. Some studies have shown a strong epidemiological association between the ingestion of acetylsalicylic acid (ASA) during the viral infection and development of Reye's syndrome. CASE REPORT: We describe the case of a 20-month-old female who developed Reye's syndrome within the context of a viral infection and the ingestion of ASA. A hepatic biopsy study is appropriate in this syndrome. The patient presented a non-convulsive status during the acute phase and at one year developed Lennox-Gastaut syndrome. She died from pneumonia at the age of 18 years. CONCLUSIONS: In all patients with clinical features that suggest Reye's syndrome, inborn errors of metabolism that can mimic it must be precluded. Although the incidence of this syndrome has gone down considerably in recent years, it is important to keep it in mind as an early and aggressive diagnosis and treatment of cerebral hypertension will reduce the mortality rate and the sequelae.

Síndrome de Reye. Descripción de un caso con especial interés en sus crisis epilépticas / Reye's syndrome. Description of a case focused on the patient's epileptic seizures

Introducción. El síndrome de Reye es una enfermedad aguda caracterizada por encefalopatía y degeneración grasa del hígado que ocurre casi exclusivamente en niños. Puede dar lugar al fallecimiento del paciente hasta en un tercio de los casos, generalmente por edema cerebral grave. La etiopatogenia de este cuadro es incierta, suele precederse de una infecciónviral generalmente por el virus de influenza o varicela. Hay estudios que han demostrado una fuerte asociación epidemiológica entre la ingestión de ácido acetilsalicílico (AAS) durante la infección viral y el desarrollo del síndrome de Reye. Caso clínico.Niña de 20 meses que desarrolla un síndrome de Reye en el contexto de cuadro viral e ingesta de AAS. La biopsia hepática es congruente con el síndrome. Presenta un estatus no convulsivo durante la fase aguda y al año desarrolla un síndrome de Lennox-Gastaut. Fallece a los 18 años por neumonía. Conclusiones. En todo paciente con clínica sugerente de síndrome de Reye, habrá que descartar errores congénitos del metabolismo que lo pueden imitar. Aunque la incidencia de este síndrome hadisminuido considerablemente en los últimos años, es importante tenerlo aún en mente, ya que un diagnóstico y tratamiento precoz y agresivo de la hipertensión cerebral disminuirá la mortalidad y las secuelas

Introduction. Reye’s syndrome is an acute disease characterised by encephalopathy and fatty degeneration of the liver that occurs almost exclusively in children. It can cause the death of the patient in up to a third of all cases, generally due to severe cerebral oedema. The aetiopathogenesis of this condition is uncertain and is usually preceded by a viral infection,generally from the influenza or varicella virus. Some studies have shown a strong epidemiological association between the ingestion of acetylsalicylic acid (ASA) during the viral infection and development of Reye’s syndrome. Case report. We describe the case of a 20-month-old female who developed Reye’s syndrome within the context of a viral infection and theingestion of ASA. A hepatic biopsy study is appropriate in this syndrome. The patient presented a non-convulsive status during the acute phase and at one year developed Lennox-Gastaut syndrome. She died from pneumonia at the age of 18 years. Conclusions. In all patients with clinical features that suggest Reye’s syndrome, inborn errors of metabolism that can mimic it must be precluded. Although the incidence of this syndrome has gone down considerably in recent years, it is important to keep it in mind as an early and aggressive diagnosis and treatment of cerebral hypertension will reduce the mortality rate and the sequelae