Post-surgical effects on language in patients with presumed low-grade glioma.

OBJECTIVES: Low-grade glioma (LGG) is a slow-growing brain tumour often situated in or near areas involved in language and/or cognitive functions. Thus, language impairments due to tumour growth or surgical resection are obvious risks. We aimed to investigate language outcome following surgery in patients with presumed LGG, using a comprehensive and sensitive language assessment. MATERIALS AND METHODS: Thirty-two consecutive patients with presumed LGG were assessed preoperative, early post-operative, and 3 months post-operative using sensitive tests including lexical retrieval, language comprehension and high-level language. The patients' preoperative language ability was compared with a reference group, but also with performance at post-operative controls. Further, the association between tumour location and language performance pre- and post-operatively was explored. RESULTS: Before surgery, the patients with presumed LGG performed worse on tests of lexical retrieval when compared to a reference group (BNT: LGG-group median 52, Reference-group median 54, P = .002; Animals: LGG-group mean 21.0, Reference-group mean 25, P = 001; Verbs: LGG-group mean 17.3, Reference-group mean 21.4, P = .001). At early post-operative assessment, we observed a decline in all language tests, whereas at 3 months there was only a decline on a single test of lexical retrieval (Animals: preoperative. median 20, post-op median 14, P = .001). The highest proportion of language impairment was found in the group with a tumour in language-eloquent areas at all time-points. CONCLUSIONS: Although many patients with a tumour in the left hemisphere deteriorated in their language function directly after surgery, their prognosis for recovery was good.

Prognostic capacity of automated quantification of suppression time in the EEG of post-asphyctic full-term neonates.

AIM: To evaluate the prognostic capacity of a new method for automatic quantification of the length of suppression time in the electroencephalogram (EEG) of a group of asphyxiated newborn infants. METHODS: Twenty-one full-term newborn infants who had been resuscitated for severe birth asphyxia were studied. Eight channel continuous EEG was recorded for prolonged time periods during the first days of life. Artefact detection or rejection was not applied to the signals. The signals were fed through a pretrained classifier and then segmented into burst and suppression periods. Total suppression length per hour was calculated. All surviving patients were followed with structured neurodevelopmental assessments to at least 18 months of age. RESULTS: The patients who developed neurodevelopmental disability or died had significant suppression periods in their EEG during the first days of life while the patients who had a normal follow-up had no or negligible amount of suppression. CONCLUSIONS: This new method for automatic quantification of suppression periods in the raw, neonatal EEG discriminates infants with good from those with poor outcome.

Does indomethacin for closure of patent ductus arteriosus affect cerebral function?

OBJECTIVE: To study whether indomethacin used in conventional dose for closure of patent ductus arteriosus affects cerebral function measured by electroencephalograms (EEG) evaluated by quantitative measures. STUDY DESIGN: Seven premature neonates with haemodynamically significant persistent ductus arteriosus were recruited. EEG were recorded before, during and after an intravenous infusion of 0.2 mg/kg indomethacin over 10 min. The EEG was analysed by two methods with different degrees of complexity for the amount of low-activity periods (LAP, "suppressions") as an indicator of affection of cerebral function. RESULTS: Neither of the two methods identified any change in the amount of LAPs in the EEG as compared to before the indomethacin infusion. CONCLUSION: Indomethacin in conventional dose for closure of patent ductus arteriosus does not affect cerebral function as evaluated by quantitative EEG.

Classification of burst and suppression in the neonatal electroencephalogram.

Fisher's linear discriminant (FLD), a feed-forward artificial neural network (ANN) and a support vector machine (SVM) were compared with respect to their ability to distinguish bursts from suppressions in electroencephalograms (EEG) displaying a burst-suppression pattern. Five features extracted from the EEG were used as inputs. The study was based on EEG signals from six full-term infants who had suffered from perinatal asphyxia, and the methods have been trained with reference data classified by an experienced electroencephalographer. The results are summarized as the area under the curve (AUC), derived from receiver operating characteristic (ROC) curves for the three methods. Based on this, the SVM performs slightly better than the others. Testing the three methods with combinations of increasing numbers of the five features shows that the SVM handles the increasing amount of information better than the other methods.

Comparing a supervised and an unsupervised classification method for burst detection in neonatal EEG.

Hidden Markov Models (HMM) and Support Vector Machines (SVM) using unsupervised and supervised training, respectively, were compared with respect to their ability to correctly classify burst and suppression in neonatal EEG. Each classifier was fed five feature signals extracted from EEG signals from six full term infants who had suffered from perinatal asphyxia. Visual inspection of the EEG by an experienced electroencephalographer was used as the gold standard when training the SVM, and for evaluating the performance of both methods. The results are presented as receiver operating characteristic (ROC) curves and quantified by the area under the curve (AUC). Our study show that the SVM and the HMM exhibit similar performance, despite their fundamental differences.

Comparison of three methods for classifying burst and suppression in the EEG of post asphyctic newborns.

Fisher's linear discriminant, a feed-forward neural network (NN) and a support vector machine (SVM) are compared with respect to their ability to distinguish bursts from suppression in burst-suppression electroencephalogram (EEG) signals using five features inherent in the EEG as input. The study is based on EEG signals from six full term infants who have suffered from perinatal asphyxia, and the methods have been trained with reference data classified by an experienced electroencephalographer. The results are summarized as area under the curve (AUC) values derived from receiver operating characteristic (ROC) curves for the three methods, and show that the SVM is slightly better than the others, at the cost of a higher computational complexity.

Spectral distance for ARMA models applied to electroencephalogram for early detection of hypoxia.

A novel measure of spectral distance is presented, which is inspired by the prediction residual parameter presented by Itakura in 1975, but derived from frequency domain data and extended to include autoregressive moving average (ARMA) models. This new algorithm is applied to electroencephalogram (EEG) data from newborn piglets exposed to hypoxia for the purpose of early detection of hypoxia. The performance is evaluated using parameters relevant for potential clinical use, and is found to outperform the Itakura distance, which has proved to be useful for this application. Additionally, we compare the performance with various algorithms previously used for the detection of hypoxia from EEG. Our results based on EEG from newborn piglets show that some detector statistics divert significantly from a reference period less than 2 min after the start of general hypoxia. Among these successful detectors, the proposed spectral distance is the only spectral-based parameter. It therefore appears that spectral changes due to hypoxia are best described by use of an ARMA- model-based spectral estimate, but the drawback of the presented method is high computational effort.

Detection of bursts in the EEG of post asphyctic newborns.

Eight features inherent in the electroencephalogram (EEG) have been extracted and evaluated with respect to their ability to distinguish bursts from suppression in burst-suppression EEG. The study is based on EEG from six full term infants who had suffered from lack of oxygen during birth. The features were used as input in a neural network, which was trained on reference data segmented by an experienced electroencephalographer. The performance was then evaluated on validation data for each feature separately and in combinations. The results show that there are significant variations in the type of activity found in burst-suppression EEG from different subjects, and that while one or a few features seem to be sufficient for most patients in this group, some cases require specific combinations of features for good detection to be possible.

Infraslow EEG activity in burst periods from post asphyctic full term neonates.

OBJECTIVE: To investigate whether very low EEG frequency activity can be recorded from post asphyctic full term neonates using EEG equipment where the high pass filter level was lowered to 0.05 Hz. METHODS: The time constant of the amplifier hardware was set to 3.2 s in order to enable recordings that equal to a high pass filter cut off at 0.05 Hz. Burst episodes were selected from the EEGs of 5 post asphyctic full term neonates. The episodes were analysed visually using different montages and subjected to power spectrum analysis. Powers in two bands were estimated; 0-1 and 1-4 Hz, designated very low- and low-frequency activity, respectively (VLFA, LFA). RESULTS: In all infants, VLFA coinciding with the burst episodes could be detected. The duration of the VLFA was about the same as that of the burst episode i.e. around 4s. The activity was most prominent over the posterior regions. In this small material, a large amount of VLFA neonatally seemed to possibly be related to a more favourable prognosis. CONCLUSIONS: VLFA can be recorded from post asphyctic full term neonates using EEG equipment with lowered cut off frequency for the high pass filter. SIGNIFICANCE: VLFA normally disregarded due to filtering, is present in the EEG of sick neonates and may carry important clinical information.

Spectral analysis of burst periods in EEG from healthy and post-asphyctic full-term neonates.

OBJECTIVE: To investigate whether the periodic EEG patterns seen in healthy and sick full term neonates (trace alternant and burst suppression, respectively) have different frequency characteristics. METHODS: Burst episodes were selected from the EEGs of 9 healthy and 9 post-asphyctic full-term neonates and subjected to power spectrum analysis. Powers in two bands were estimated; 0-4 and 4-30 Hz, designated low- and high-frequency activity, respectively (LFA, HFA). The spectral edge frequency (SEF) was also assessed. RESULTS: In bursts, the LFA power was lower in periods of burst suppression as compared to those of trace alternant. The parameter that best discriminated between the groups was the relative amount of low- and high-frequency activity. The SEF parameter had a low sensitivity to the group differences. In healthy neonates, the LFA power was higher over the posterior right as compared to the posterior left region. CONCLUSIONS: Spectral power of low frequencies differs significantly between the burst episodes of healthy and sick neonates. SIGNIFICANCE: These results can be used when monitoring cerebral function in neonates.

Long-term effects of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) was studied both after experimental induction in rats and spontaneously occurring in man. The growth-retarded rat pups were compared to appropriately grown litter mates with developmental and behavioural tests at 50 and 90 days of age. Female rats exhibited no differences between growth-retarded and control rats but growth-retarded male rats had poor performance at 50 but not at 90 days compared to male controls. In the patient study 25 growth-retarded babies were compared with 21 appropriately grown controls. The growth-retarded babies had delayed latency periods of the visual evoked potentials at term and 6 weeks later, and at follow-up (18 months) demonstrated significantly more developmental and behavioural problems than the control group.

Scavengers of free oxygen radicals in combination with magnesium ameliorate perinatal hypoxic-ischemic brain damage in the rat.

The effect of oxygen radical scavengers in combination with magnesium administered after a hypoxic-ischemic insult was evaluated in a model of perinatal brain damage. A mixture of scavengers of oxygen-derived free radicals (L-methionine, 0.2 g; mannitol, 0.5 g) and magnesium sulfate (0.3 g) per kg body weight was given to 34 1-wk-old rat pups immediately after a session of unilateral carotid artery ligation and 2 h of hypoxia (8% O2 in N2). Thirty-four littermates served as controls; they received a placebo. At 3 wk of age, there was a significantly smaller reduction of hemisphere weight ipsilateral to the ligation in the treated animals compared with the controls (0.7 versus 8.8% of contralateral hemisphere weight median values, p < 0.01). The difference was especially marked for the most severe degrees of brain damage. Only one of the 34 treated animals, compared with 13 of 34 control animals, had a reduction of ipsilateral hemisphere weight > 25%. The protection offered by the mixture used was larger than in previously published studies using this model and treatment after the hypoxic exposure with only one protective agent. It is concluded that a combination of oxygen radical scavengers and magnesium administered in the phase of resuscitation mitigates perinatal postasphyxial brain damage in the rat. An additive protective effect of different therapeutic strategies on the brain damage may be present in this situation.

Cerebral amino acids and energy metabolites in the growth retarded rat fetus under normoxia and hypoxia.

The effect of intrauterine growth retardation (IUGR) on striatal energy metabolites and amino acid concentrations was studied in the fetuses of eight nulliparous rat dams after uterine artery ligation on day 18 of gestation. On day 22 (term = 23), four dams were subjected to normoxia and four to hypoxia (10% oxygen) for 58 min, while monitoring hemodynamics and blood gases. After decapitation of the dam, fetuses were delivered by sectio and decapitated. The measured parameters in the dams were stable under normoxia but exhibited decreased oxygen availability under hypoxia. Striatal energy balance was preserved in IUGRs, both under maternal normoxic and hypoxic conditions, compared to appropriately grown (AGA) littermates. Under maternal normoxia, the striatal concentration of aspartate was reduced (P < 0.01) in IUGRs and the level of alanine was increased (P < 0.01) as compared to AGAs. Under hypoxia, the level of GABA was higher in IUGRs (P < 0.01). Lactate was increased in all fetuses under hypoxia. It is concluded that striatal energy metabolism is preserved in IUGR rat fetuses in late gestation under both maternal normoxia and hypoxia. Amino acid metabolism, however, is disturbed and depends on the degree of growth retardation and on the severity of perinatal stress.

Cerebral and adrenal monoamine metabolism in the growth-retarded rat fetus under normoxia and hypoxia.

The effect of intrauterine growth retardation (IUGR) on cerebral and adrenal monoamine metabolism was studied in the fetuses of eight nulliparous rat dams after unilateral uterine artery ligation on d 18 of gestation. On d 22 (term = 23 d), four dams were subjected to normoxia and four to hypoxia (10% O2) for 58 min while their hemodynamics and blood gases were monitored. An inhibitor of L-aromatic-decarboxylase (3-hydroxybensylhydrazine) was infused to measure monoamine synthesis rate. After decapitation of the dam, fetuses were delivered by sectio, decapitated, and dissected at -5 degrees C. The body, liver, forebrain, brainstem, and adrenal glands were weighed, and concentrations of monoamine precursors, transmitters, and metabolites were assessed in the three latter organs. The weights of liver and forebrain were reduced in fetuses with IUGR, whereas brainstem and adrenal weights were unaltered. Epinephrine content in adrenals was reduced in proportion to body weight under normoxia but failed to increase under hypoxia as it did in appropriately grown fetuses. There were only minor changes in monoamine metabolism in the brainstem. In the forebrain, however, marked changes were seen, mainly in serotonin metabolism: under normoxia, fetuses with IUGR had decreased levels of serotonin and its metabolite 5-hydroxyindole acetic acid. Under hypoxia, appropriately grown fetuses reduced their concentrations of these substances, whereas fetuses with IUGR paradoxically increased their synthetic activity. It is concluded that a disturbance of central nervous serotonin metabolism prevails in growth-retarded rat fetuses in late gestation and that this disturbance depends on the degree of growth retardation and the degree of perinatal stress.

Cerebral lipid peroxidation in the growth retarded rat fetus under normoxia and hypoxia.

To detect a possible relationship between the increased vulnerability of the brain of the growth retarded fetus and lipid peroxidation, the activity of the latter was investigated in the forebrain of rat fetuses on day 22 of gestation (term = 23). Growth retardation was induced by uterine artery ligation on day 18. The susceptibility of the forebrain to lipid peroxidation was analysed using the thiobarbituric acid technique after exposure of the awake dams to room air or hypoxia (10% O2) for 58 minutes. Hemodynamics and blood gas status in the dams were stable under conditions of normoxia. When exposed to hypoxia, oxygen availability decreased and blood pressure fell slightly. When normalised for litter, lipid peroxidation covaried with fetal weight in fetuses from normoxic dams, only when Fe2+ (a promotor of lipid peroxidation) was added in the incubation. In fetuses from hypoxic dams, this relationship existed irrespective of whether Fe2+ was present during incubation. In all of these associations, smaller fetuses exhibited more intense lipid peroxidation. In the perinatal period, an increased vulnerability of the central nervous system prevails in growth retarded individuals. An increased tendency to undergo lipid peroxidation and/or a weak defence against this process may be part of the pathophysiologic background.

Cerebral function in the growth-retarded fetus and neonate.

Intrauterine growth retardation is associated with increased risks for permanent neurological disabilities. A series of studies was undertaken to elucidate whether fetal growth retardation causes a primary perturbation of brain function and development and whether an increased vulnerability for periods of oxygen lack exists. In two groups of neonates who were small for gestational age (SGA) evoked potentials were investigated. A high frequency of abnormal recordings were obtained in SGA babies. SGA babies had significantly longer latency periods for the primary evoked potentials than appropriately grown controls. In guinea pigs and rats growth retardation was induced by reducing the placental blood flow during late gestation. Growth retarded guinea pups demonstrated a considerable reduction of the ability to retain normal somatosensory evoked response during hypoxia compared to appropriately grown littermates. Growth retarded rat fetuses exhibited marked changes of the monoamine metabolism in the brain inasmuch as basal levels of serotonin and its main metabolite were low while an inappropriate acceleration of the serotonin synthesis rate took place during hypoxia. The tissue concentrations of aspartate were also significantly lower in growth retarded fetuses than normally grown littermates. Finally, lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation in brain tissue of growth retarded and appropriately grown fetuses was compared but during mild-moderate hypoxia lipid peroxidation was significantly more intense in the growth retarded group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral function of the guinea pig neonate after chronic intrauterine exposure to khat (Catha edulis Forsk.).

Cerebral function in normoxia and its reactions to standard periods of hypoxia of increasing severity were studied in 30 newborn guinea pigs less than 3 days old. Intrauterine growth retardation was induced either by uterine artery ligation at midgestation or by feeding the female in late gestation with khat leaves, an amphetamine-like stimulant chewed by men and women in several countries in eastern Africa and Arabia. After spontaneous delivery, the neonates were anesthetized and ventilated. Cardiovascular, metabolic, and neurophysiologic (somatosensory evoked potentials) parameters were monitored. Under normoxia, the khat-exposed group showed prolonged latency of the primary response of the somatosensory evoked potentials and a reduced amount of secondary components. Under hypoxia, this group also has a greater reduction of amplitude of the somatosensory evoked potentials. It is concluded that khat exposure during fetal life has an impact on the cerebral function during the neonatal period (at least up to 3 days of age) which is not solely explained by the concomitantly produced growth retardation.

Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia.

In spite of improvements in obstetric and neonatal care, hypoxic-ischemic brain damage with severe neurologic disability is still a clinical reality. A model in 7-day-old rats has been introduced to study the pathophysiology of perinatal hypoxic-ischemic brain damage. Unilateral brain damage is produced in the cerebral cortex, striatum and hippocampus, i.e. a similar distribution as is often seen in human asphyxiated neonates. In the present investigation the model was evaluated further by comparing three different methods to assess the brain damage: weighing the hemispheres, morphometry and somatosensory evoked potentials. Seven-day-old rats were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (7.7% O2 at 36 degrees C). After 2 h of hypoxic-ischemia pCO2 and pO2 decreased in mixed arterial/venous blood. The evaluation of the damage 2 weeks after the insult, demonstrated close correlation between morphometry and weighing (r = 0.836, P less than 0.01). The amplitude of evoked potentials correlated to the other parameters (r = 0.814, P less than 0.01 and r = 0.824, P less than 0.01 respectively) and displayed a greater relative attenuation than the other methods but with a more pronounced variability. These results indicate that the degree of brain damage can be assessed by weighing for screening purposes.

Cerebral tolerance of hypoxia in growth-retarded and appropriately grown newborn guinea pigs.

To elucidate if there is a reduced perinatal tolerance of hypoxia in growth retardation and approach its pathophysiologic background, newborn guinea pigs of different weights were subjected to standardized hypoxia. Intrauterine growth retardation was induced through uterine artery ligation. After spontaneous delivery experiments were performed within 2 days. After stabilization, hypoxia of stepwise increased severity was instituted. Blood gases, metabolic, cardiovascular, and neurophysiologic [somatosensory-evoked potentials (SEP)] parameters were monitored. A control series in which equally large blood samples were taken at the same intervals was performed. The animals were grouped according to birth weight: greater than or equal to 101 g (n = 10, 12), 71-100 g (n = 11, 10), and less than or equal to 70 g (n = 8, 3) (hypoxic and control series, respectively). Basal SEP latencies did not differ between the groups. Under hypoxia, both the amplitude of the SEP and the time to complete loss of the SEP was reduced in proportion to the degree of growth retardation. The differences between all groups were significant. The animals in the control series did not change their SEP performance significantly. Slight differences in metabolic and cardiovascular parameters between the groups were found not likely to explain the differences in SEP performance. Therefore, it is concluded that a reduced cerebral tolerance of hypoxia prevails in growth-retarded newborn guinea pigs and that this is related to changes in the brain itself. It is also concluded that a relationship exists between the degree of growth retardation and that of reduced cerebral hypoxia tolerance.