18F fluorodeoxyglucose (18FDG) and positron tomography (PT) were used in 20 full term babies with seizures or hypotonia to describe regional cerebral glucose metabolism. Among babies with seizures, birth asphyxia was the most common cause. PT was performed at age 6-17 days. One hour before PT, 18FDG (50-100 microCi/kg) was injected intravenously. Ten or more PT sections were obtained in each infant. The areas of the brain that were metabolically the most active were the cortex and the thalami. Six cortical areas and a white matter reference area were selected for analysis of relative rates of glucose metabolism as indicated by relative rates of fluorine-18 activity. Cortical fluorine-18 activity was highest in the pericentral (sensorimotor) regions and lowest in the frontal regions. The overall cortex/white matter ratio for fluorine-18 activity averaged 1.78 +/- 0.44 (SD). Four patterns of regional cerebral glucose metabolism were distinguished: 1) bilateral symmetry, 2) loss of metabolic definition, 3) hemispheral asymmetry, 4) focal hyper- or hypometabolism. Patterns 1) and 2) correlated with a history of birth asphyxia, a diagnosis of hypoxic-ischemic encephalopathy and the absence of focal echoes on cranial ultrasound. Hypodense areas on CT could be associated with either high or low fluorine-18 relative activity on PT. The prognostic significance of the presently reported patterns of cerebral glucose metabolism remains to be determined.

The increasing number of studies demonstrates the high potency of the intrathecal (IT) route for the delivery of biopharmaceuticals to the central nervous system (CNS). Our earlier data exhibited that both the infused volume and the infusion rate can regulate the initial disposition of the administered solute within the cerebrospinal fluid (CSF). This disposition is one of key factors in defining the subsequent transport of the solute to its intended target. On the other hand, fast additions of large volumes of liquid to the CSF inevitably raise the CSF pressure [a.k.a. intracranial pressure (ICP)], which may in turn lead to adverse reactions if the physiologically delimited threshold is exceeded. While long-term biological effects of elevated ICP (hydrocephalus) are known, the safety thresholds pertaining to short-term ICP elevations caused by IT administrations have not yet been characterized. This study aimed to investigate the dynamics of ICP in rats and non-human primates (NHPs) with respect to IT infusion rates and volumes. The safety regimes were estimated and analyzed across species to facilitate the development of translational large-volume IT therapies. The data revealed that the addition of a liquid to the CSF raised the ICP in a rate and volume-dependent manner. At low infusion rates (<0.12 ml/min in rats and <2 ml/min in NHPs), NHPs and rats displayed similar tolerance patterns. Specifically, safe accommodations of such added volumes were mainly facilitated by the accelerated pressure-dependent CSF drainage into the blood, with I stabilizing at different levels below the safety threshold of 28 ± 4 mm Hg in rats and 50 ± 5 mm Hg in NHPs. These ICPs were safely tolerated for extended durations (of at least 2–25 min). High infusion rates (including boluses) caused uncompensated exponential ICP elevations rapidly exceeding the safety thresholds. Their tolerance was species-dependent and was facilitated by the compensatory role of the varied components of craniospinal compliance while not excluding the possibility of other contributing factors. In conclusion, large volumes of liquids can safely be delivered via IT routes provided that ICP is monitored as a safety factor and cross-species physiological differences are accounted for.

SUMMARY Cerebrospinal fluid (CSF) myelin basic protein (MBP) was measured blind by double antibody competitive inhibition radioimmunoassay (RIA) in 20 children who had seizures and 17 children with hydrocephalus. MBP values correlated with clinical outcome and mean maximum intracranial pressure (ICP) in the hydrocephalic group, and with type of convulsion in the epileptic group. A value of 20ng/ml or more was regarded as significantly raised. A significant rise in MBP levels could be demonstrated in those with ICP alone and in patients with additional problems, whose levels tended to be even higher. Hydrocephalic children with normal ICP and children with seizures had similar normal MBP levels, and in the latter group clinical outcome was not related to MBP levels. For individual patients CSF MBP is of little value as a prognostic indicator, or as a method of quantifying cerebral damage. RÉSUMÉ Réaction immunitaire des protéines myéliniques de base du liquide céphalorachidien comme indicaleur de lésions cerebrates chez l'enfant Les protéines myéliniques de base (MBP) ont été mesurées dans le liquide céphalo‐rachidien (LCR) en aveugle par recherche radio‐immunitaire établie par inhibition compétitive sur double anticorps (RIA), chez 20 enfants présentant des crises et chez 17 enfants hydrocéphales. Les valeurs MBP étaient corrélées avec le devenir clinique et la moyenne des pressions intra‐crâniennes maximales (ICP) dans le groupe hydrocéphale et avec le type de convulsions dans le groupe épileptique. Une valeur de 20 ng/ml ou plus fut considérée comme significativement élevée. Une élévation significative des taux de MBP a pu être démontrée chez les sujets avec ICP élevée isolée et chez les sujets avec problèmes ajoutés, les taux tendant alors àêtre même plus eleves. Les enfants hydrocephales avec ICP normale et les enfants avec crises avaient semblablement des taux normaux de MBP et dans ce dernier groupe clinique, le devenir clinique n'etait pas relié au taux de MBP. Chez les sujets individuels, le MBP du LCR est de peu de valeur comme indicateur pronostic ou comme méthode pour quantifier le dommage cérébral. ZUSAMMENFASSUNG Immunoreaktivität des basischen Myelinproteins aus dem Liquor als Indikator fur eine Schädigung des Gehirns bei Kindern Bei 20 Kindern mit einem Anfallsleiden und 17 mit Hydrocephalus wurde das basische Myelinprotein (MBP) im Liquor (CSF) mit einem Doppelantikörper‐Radioimmunoassay (RIA) bestimmt. Bei der Gruppe mit Hydrocephalus korrelierten die MBP‐Werte mit dem klinischen Ergebnis und dem mittleren maximalen intracraniellen Druck (ICP), bei der Epilepsiegruppe korrelierten sie mit dem Krampftyp. Ein Wert von 20ng/ml oder mehr wurde als signifikant erhöht angesehen. Ein signifikanter Anstieg der MBP‐Spiegel konnte bei den Kindern mit ICP und bei Patienten mit zusäzlichen Problemen nachgewiesen werden, deren Spiegel in der Regel noch höher waren. Hydrocephale Kuder mit normalem ICP und Kinder mit Anfällen hatten ähnlich normale MBP‐Spiegel und in der letzten Gruppe bestand keine Korrelation...

SUMMARY Intracranial pressure and cerebrospinal fluid hypoxanthine and xanthine concentrations were measured in hydrocephalic children with suspected raised intracranial pressure. There was a highly significant correlation between intracranial pressure and cerebrospinal fluid hypoxanthine and xanthine levels.Adenosine triphosphate (ATP) is the main energy currency of the cell.' Adenine nucleotides are catabolised during failure of energy supply2 to uncharged products which can escape from the ce113-8 so that hypoxanthine69 1015 and xanthine'5 concentrations rise in extracellular fluid, for example, cerebrospinal fluid (CSF). The breakdown of GTP contributes to the related increase in xanthine excretion.22 The raised hypoxanthine and xanthine concentrations in CSF from ATP and GTP breakdown in brain can be measured.'3 1" The high and irreducible" energy consumption of the brain renders it especially vulnerable to failures of oxygen or glucose supply, both of which are reduced in ischaemia. Such ischaemia occurs with raised intracranial pressure (ICP). '6 Previous studies have shown that brief intracranial pressure monitoring in the awake hydrocephalic patient is likely to produce a false low normal measurement because of the patient's ability to regulate pressure by hyperventilating."' Overnight pressure studies have shown that ICP is highest during REM sleep.'9 These studies are time-consuming and invasive but may be justified because of limitations in the diagnosis of raised ICP from imaged ventricular dilatation. A biochemical marker indicating that