Glycosphingolipid expression in cerebrospinal fluid of infants with neurological abnormalities: report of three cases.

The aim of this study was to analyse glycosphingolipid expression in cerebrospinal fluid (CSF) from one idiopathic West syndrome (IWS) infant, one with Reye like syndrome, and one with congenital hydrocephalus, in comparison to control group (n=7) using highly sensitive thin-layer chromatography-immunostaining methods. Gangliotetraose-series gangliosides (acidic glycosphingolipids) were not detected in CSF of infant with idiopathic West syndrome and infant with congenital hydrocephalus. CSF of infant with IWS showed traces of neolacto-tetraose ganglioside fractions, which were absent in all other CSF examined. In addition, lactosylceramide fraction, and one ceramide fraction were highly expressed only in IWS CSF These results confirmed previously described lack of gangliotetraose-series gangliosides in IWS patient and for the first time is described increased expression of neolacto-series glycosphingolipids in IWS patient. Since follow up until the age of five years showed almost normal IWS patient psychomotor development, the discribed shift of glycosphingolipid expression may implicate on transient inhibition of specific glycosyl transferases in the age of seven months.

El síndrome de Reye: reporte de ocho casos en el servicio de pediatria del Hospital Regional Docente "Ambato" / Reye's syndrome: report of 8 cases at the servicio de pediatria del Hospital Regional Docente Ambato

Se reportan 8 casos de Sindrome de Reye diagnosticados y tratados en el Servicio de Pediatría del Hospital Regional "Ambato" cuya edad media fue de 7,6 años con un rango entre 1 y 12. La mitad de los pacientes fueron varones y el 75% del total procedían de medio rural. Un porcentaje igual mostró signos de desnutrición con un déficit promedio de peso del 21,36% en relación a la edad. El antecedente de infección respiratoria o digestiva previa fue positiva en 6 niños y el intervalo entre aquel y el comienzo de los síntomas, de 10 días. Seis niños se recuperaron, en 4 fue total, uno quedó con ceguera cortical y otro con alteraciones del EEG, pero clínicamente asintomático. Dos niños fallecieron y la autopsia confirmó el diagnóstico de la enfermedad. El Síndrome de Reye representó entre el 1 y 4 por mil de los egresos del Servicio de Pediatría del Hospital Regional Ambato y las cifras más elevadas han coincidido con los brotes de influenza que se han presentado en nuestra ciudad. Se hace incapié en el hecho de que el diagnóstico precoz de la enfermedad es de gran importancia pues el tratamiento sencillo que requiere al comienzo puede hacer revertir la enfermedad de su curso indiscutiblemente grave

Influenza B-associated Reye syndrome: report of a case with isolation of a coxsackie A5 virus from CSF.

A 16 month old girl developed Reye syndrome a few days after an episode of influenza. The diagnosis of RS was made on clinical and laboratory data. Virological examinations were done on specimens of stools, throat swab, spinal fluid and two samples of serum. A coxsackievirus A5 was isolated from the spinal fluid. A seroconversion was found against the variant of influenza type B virus circulating in our region at that time and the isolated coxsackie A5 strain. The involvement in the CNS of coxsackie A5 and the demonstration of a simultaneous infection with influenza B virus supports the hypothesis that a mixed viral infection could trigger the Reye syndrome.

Intravenous glycerol and mannitol therapy in children with intracranial hypertension.

Acute intracranial hypertension may respond to intravenous mannitol, but frequent administration can cause cerebral edema or renal problems. We evaluated the use of 20% glycerol administered intravenously as an alternative to mannitol. Intravenous glycerol and mannitol were equally effective in lowering acute elevations of intracranial pressure. The duration of effect was similar for both agents. Side effects of intravenous glycerol were related to concentration, rate, and frequency of administration. In severe encephalopathies, such as Reye syndrome, we recommend infusions of 20% glycerol or 20% mannitol at a dose of 0.5-1.0 gm per kilogram. Glycerol should be administered in 0.45% or 0.9% saline, no faster than 1.5 ml (3.3 mOsm) per minute.

Sindrome de Reye: criterios diagnosticos, secuelas neurologicas / Reye's Syndrome: diagnosis criteria, neurological sequels

El sindrome de Reye, se considera enfermedad poco comun entre adultos. Presentamos el cuarto caso informado en el pais y el primero que se recupera. Se trata de una mujer de 18 anos, quien con un diagnostico de "Hepatitis Viral", ingresa en estado de estupor, presenta vomito pertinaz y evoluciona al coma superficial, se le observa ademas hematosis, convulsiones focales y posteriormente se recupera. El reconocimiento precoz del sindrome se hace mediante la aplicacion de los criterios diagnosticos, la ayuda del laboratorio y hallazgos asociados que estan bien documentados en esta enfermedad.

Reye syndrome: monoamine metabolites in ventricular fluid.

Concentrations of homovanillic acid (HVA) were markedly elevated in the ventricular fluid of 15 children with Reye syndrome (median, 887 ng per milliliter) compared to 7 controls (median, 282 ng per milliliter), but 5-hydroxyindoleacetic acid (5-HIAA) values were comparable (medians of 198 and 189 ng per milliliter, respectively). The ratio of 5-HIAA to HVA was significantly lower in patients with Reye syndrome (0.26) than in controls (0.51). Serial samples demonstrated wide fluctuations in HVA concentration, but not in that of 5-HIAA. Monoamine metabolite concentrations were not correlated with serum ammonia, increased intracranial pressure, morbidity, or mortality. Increased HVA in Reye syndrome may reflect cerebral ischemia and release of vasoactive amines (particularly dopamine) into the brain and cerebrospinal fluid (CSF).

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.

Studies on the pathophysiology of encephalopathy in Reye's syndrome; Hyperammonemia in Reye's syndrome.

The initial acid-base status of eight survivors of Reye's syndrome was characterized by acute respiratory alkalosis (Pco2=32 mm Hg; Hco3-=22.0 mEq/liter) while that of eight children who died was associated with metabolic acidosis as well (HCO3-=10.0 mEg/liter). Arterial-internal jugular venous ammonia concentration differences on day 1 (299 mg/100 ml) and day 2 (90 mg/100 ml) reflected cerebral uptake of ammonia while those on days 3 and 4 (-43 and -55 mg/100 ml) demonstrated cerebral release. Arterial blood hyperammonemia can be detoxified safely in the brain as long as the levels do not exceed approximately 300mug/100 ml. Beyond that level lactic acidosis is observed, particularly in cerebral venous drainage. Arterial blood hyperammonemia was also related to the extent of alveolar hyperventilation. These findings are very similar to those seen in experimental hyperammonemia and support the concept that neurotoxicity in children with Reye's syndrome is at least partly due to impaired oxidative metabolism secondary to hyperammonemia.

Possible pathogenic role of endotoxin in Reye's syndrome.

Evidence of circulating endotoxin was sought in children with Reye's syndrome, on the thesis that severe hepatic failure is likely to result in loss of capacity to detoxify intestinal endotoxins entering the circulation. A modification of the Limulus assay was used to demonstrate high levels of endotoxin-like activity (E.L.A.) in nine comatose patients with Reye's syndrome and in one of the two non-comatose patients. The symptom-free sibling of one patient had raised liver enzymes and a negative Limulus test. Plasma E.L.A. correlated significantly with degree of electroencephalographic disturbance early in the course of the illness. E.L.A. was also found in both of two cerebrospinal fluids evaluated. Preliminary in-vitro characterisation of this substance indicated that it resembled endotoxin derived from anaerobic intestinal bacteria. Intestinally derived endotoxin could be one factor in the pathogenesis of encephalopathy and other features of Reye's syndrome.

Reye's syndrome.

Although frequently unrecognized, Reye's syndrome is a significant cause of serious illness and death in children. Erroneous diagnoses include gastroenteritis, meningoencephalitis, metabolic encephalopathy, drug overdose and primary psychiatric disease. No specific cure is known but early diagnosis and vigorous empirical treatment may increase chances of survival. Although the EEG may be a useful tool in prognosis, it cannot be relied upon in deciding when to initiate or abandon aggressive therapy.