Breathing disorders during sleep and cognitive performance in an older community sample: the EVA Study.

OBJECTIVES: To determine whether poor cognitive performance was associated with symptoms related to the sleep apnea syndrome, snoring, and breathing stoppage during sleep. DESIGN: Cross-sectional analysis of data collected at baseline in the EVA Study, a 4-year cohort study. SETTING: The city of Nantes in western France. SAMPLE: A total of 1389 persons, aged 60 to 70 years, recruited from the electoral rolls of the city of Nantes. MEASUREMENTS: Demographic characteristics and data on drug use and tobacco and alcohol consumption were collected using a standardized questionnaire. Weight and height were measured. Individuals completed a previously validated sleep questionnaire about nocturnal sleep characteristics, snoring, breathing stoppage during sleep, and day-time sleepiness. Trained psychologists administered eight neuropsychological tests: The Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test of the WAIS-Revised, Benton Visual Retention Test, Paced Auditory Serial-Addition Task, Auditory Verbal Learning Test, Raven Progressive Matrices, and Word Fluency Test. Depressive symptomatology was assessed by the Center for Epidemiologic Studies-Depression scale. MAIN RESULTS: In this older sample, 49.5% of subjects reported snoring, and 10.8% reported breathing stoppage during sleep. Both respiratory disorders were associated significantly with male gender and high body mass index. In men, prevalence of snoring was increased significantly in those with alcohol consumption greater than 40 mL per day. Breathing stoppage during sleep was associated with depressive symptoms in women. Logistic regression models adjusted for age, gender, educational level, tobacco status and alcohol consumption, depressive symptomatology, and number of medications found that both snoring and breathing stoppage were associated with low scores (< or = 10th percentile) in tests requiring visual attention skills, the Trail Making Test (OR = 2.14, 95% CI = 1.24-3.69 and OR = 1.88, 95% CI = 1.04-3.39, respectively), and the Digit Symbol Substitution Test (OR = 1.80, 95% CI = 1.09-2.99 and OR = 1.58, 95% CI = .87-2.89, respectively). These relationships were significant only when either snoring or breathing stoppage was associated with daytime sleepiness. CONCLUSIONS: This cross-sectional analysis suggested that in community-dwelling individuals 60 to 70 years of age, snoring and breathing stoppage during sleep associated with daytime sleepiness were risk factors for low cognitive performance in tests requiring visual attention skills.

Lamotrigine in treatment of 120 children with epilepsy.

One hundred twenty children aged 10 months to 16 years 9 months were included in three studies with lamotrigine (LTG): a single-blind study (n = 60), a pharmacokinetic study (n = 23), and a compassionate group (n = 37). At 3 months, 11 patients had become seizure-free and 34 had > 50% decrease in seizure frequency. The best results involved absence epilepsy, Lennox-Gastaut syndrome (LGS), and other symptomatic generalized epilepsy. Forty-two patients were followed > 1 year, 22 for a mean of 2.2 years, and there was no significant increase in seizure frequency as compared with 3-month follow-up. Fourteen patients became seizure-free for > 6 months; all except 1 had generalized epilepsy. For 12 patients, treatment could be reduced to monotherapy, but for those with valproate (VPA) comedication LTG dosage had to be increased; 25% of patients with VPA monotherapy exhibited skin rash, appearing 3-18 days after starting LTG. For 4 patients, LTG could be reintroduced after VPA was withdrawn. Ten patients had ataxia and/or drowsiness and 2 had vomiting. For all other patients, tolerance was excellent.

Genetic predisposition to West syndrome.

To determine the recurrence risk of West syndrome (WS), we studied the familial antecedents of consecutively referred patients. Among siblings, there was an increased incidence of WS but not of febrile convulsions. Familial incidence of epilepsy was intermediate between the epileptic and nonepileptic control groups. When cases resulting from a genetically determined disease were excluded, incidence of epilepsy among siblings was similar to that in normal controls. Five of the 11 familial cases of WS were due to an identifiable cause: twin pregnancy, tuberous sclerosis, and recurrent maternal toxemia. In 4 of the remaining families, the clinical picture included spasms, erratic myoclonus, and postnatal microcephaly, suggestive of a previously unidentifiable progressive encephalopathy. Therefore, when identifiable familial diseases were excluded, the recurrence risk was < 1%.

Vigabatrin in childhood epilepsy.

Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic trial of vigabatrin in refractory infantile spasms.

Infantile spasms usually start during the first year of life and constitute one of the most difficult types of epilepsy to treat. They carry a very poor prognosis for both epilepsy and mental development. Seventy children, including 47 infants, with intractable infantile spasms were entered into an open study with vigabatrin as add-on therapy to the usual anticonvulsant treatment. All were resistant to previous treatments, including corticosteroids (43 patients), carbamazepine, benzodiazepines, and sodium valproate. Two children withdrew from the study because of intolerance to vigabatrin (hypotonia or hypertonia) before evaluation of efficacy could be made. Of the remaining 68 children, 29 (43%) showed complete suppression of spasms. Forty-six children had a greater than 50% reduction in spasms. The best response was observed in those with tuberous sclerosis (12/14 compared with 12/18 with symptomatic infantile spasms of other origin and 22/36 with cryptogenic infantile spasms). Following the initial response to treatment of these patients (n = 68), a long-term response was confirmed in 75% of children with symptomatic infantile spasms and 36% of children with cryptogenic infantile spasms. In eight children, all other anticonvulsant medication could be definitively withdrawn. Tolerability appeared excellent, with 52 of 70 patients reporting no side effects. Somnolence, hypotonia, weight gain, excitation, and insomnia were the most common problems at the beginning of the study and were usually transient. Given the poor prognosis of this type of childhood epilepsy, vigabatrin appears to be a very interesting advance in the management of drug-resistant infantile spasms.

Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci.

Using a quantitative in vitro model simulating clinical conditions, we studied the efficacy of conventional and nonconventional 3-day therapies involving vancomycin for treating the internal surface of catheters colonized with a slime-producing strain of Staphylococcus epidermidis. When infused for 1 hr every 8 hr through the catheter at the daily dose recommended for a 10-kg child (450 mg), vancomycin alone reduced bacterial colonization but failed to sterilize the inserts. Vancomycin was more active in combination with netilmicin (25 mg for 1 hr every 8 hr), rifampin (150 mg for 90 min every 12 hr), or fosfomycin (500 mg for 4 hr every 6 hr), but the catheters were inconsistently decontaminated after 3 days of treatment. Two nonconventional modes of antibiotic administration were tested for their capacity to ensure high levels of vancomycin in the catheter lumen over a prolonged time. Vancomycin infused continuously through the catheter at a daily dose of 450 mg had the same poor sterilizing effect as vancomycin administered intermittently. On the contrary, catheters were totally decontaminated when 2.5 mg of vancomycin in a volume of 0.5 ml were injected twice daily into noninfused catheters, confirming that the antibiotic-lock technique is an approach of great interest to sterilize the internal surface of catheters colonized with staphylococci.

Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study.

Sixty-one pediatric patients (12-229 months of age) with refractory epilepsy were treated with vigabatrin [gamma-vinyl GABA (GVG)] in a 16-week, single-blind, add-on, placebo-controlled trial. Twenty-three patients (38%) showed a reduction of more than 50% in seizure frequency; 12 patients (20%) experienced a seizure increase; and the remaining 26 did not show significant differences between placebo and GVG treatment. Among the 216 patients who entered the long-term phase after having experienced more than 50% decrease in seizure frequency, 14 continued with the same degree of improvement after 2-11 months of follow-up (mean 7.7). GVG was particularly efficient in cryptogenic partial epilepsy. Conversely, nonprogressive myoclonic epilepsy tended to be aggravated. Agitation was the most commonly observed side effect, mainly at onset of therapy in mentally retarded patients, but was easily reversed by dose reduction. GVG is a promising drug in the treatment of refractory epilepsies of childhood.

Density distribution of red cells and prognostic significance in 50 patients with homozygous sickle-cell disease.

The sickle cell disease is characterized by a heterogeneous clinical and biological expression. In order to evaluate the prognostic significance of the red blood cell density distribution: D50 (median cell density of the distribution), R60 (middle density range in which 60% of the cells can be found), F4 and F5 (proportion of cells with density higher than 1.110 and 1.120 g/ml, respectively) have been determined in 50 patients with homozygous sickle cell disease. The alpha gene status was determined in 27 patients. All patients have been included in an original score of severity fitted to infancy and childhood. A positive correlation has been found between D50 and the clinical score. This result illustrates the potential clinical importance of this parameter as well as other biological indices such as the haemoglobin F level, the alpha gene status and the haplotypes of the beta-like gene cluster.

[Critical study of erythrocyte bilirubin and predictive factors of kernicterus in premature low birth weight infants]. / Etude critique de la bilirubine érythrocytaire et des facteurs prédictifs de l'ictère nucléaire chez le prématuré de faible poids de naissance.

Among 217 premature neonates with birth-weights less than or equal to 1,500 g who died, in whom post mortem examination was carried out during the years 1978-1984, 11 cases of kernicterus (5%) were found. A comparative study was undertaken between these 11 children and 42 children of the same population matched for birth-weight, gestational age and life duration. The following clinical and biological perinatal data were found more frequently in the kernicterus group: meningitis (3/11 vs 0/42), p less than 0.01), hyperchloronatremic dehydration (3/11 vs 1/42, p less than 0.05) and hypoglycemia either severe (less than 0.83 mumol/l) (5/11 vs 3/42, p less than 0.01) or prolonged (less than 1.66 mumol/l for at least 36 hrs) (3/11 vs 0/42, p less than 0.01). The mean value of total bilirubin highest levels was 261 +/- 76 mumol/l in cases with kernicterus and 266 +/- 58 mumol/l in the control group (NS). In a case with kernicterus the total bilirubin level was 149 mumol/l (87 mg/l). Erythrocyte bilirubin was repeatedly assayed in 16 children, 4 of which were found to have kernicterus. There was no significant difference in the mean maximum peak of erythrocyte bilirubin between the 2 groups (kernicterus group: 17.8 +/- 3.4 mumol/l in the 4 cases with kernicterus. Finally, hypoglycemia, respiratory and/or metabolic acidosis were found associated with the highest erythrocyte bilirubin level, or during the 24 preceding hours in children with kernicterus only.

Influence of breathing pattern on functional residual capacity in sleeping newborn infants.

The present study was designed to assess the influence of breathing pattern on the variations of functional residual capacity during sleep in newborn infants. Functional residual capacity was measured by the He-dilution method. Neurophysiologic criteria were used to identify sleep states. Movements of chest and abdomen were monitored. Twenty-six healthy newborn infants were studied. Sixteen were premature and 10 were at term. Functional residual capacity did not change in relation to changes in sleep states. In active sleep it was 1.48 +/- 0.07 ml/cm compared with 1.50 +/- 0.06 ml/cm in quiet sleep. Functional residual capacity decreased when rib cage and abdomen moved out-of-phase with a value of 1.38 +/- 0.09 ml/cm as compared to 1.56 +/- 0.09 ml/cm when in phase (P less than 0.01), in the 7 infants who displayed these two opposite patterns.

[Comparison of 2 semi-quantitative methods for evaluating blood glucose in newborn infants]. / Comparaison de deux méthodes d'estimation semi-quantitative de la glycémie chez le nouveau-né.

Blood glucose levels were assessed in 49 neonates, using 2 blood glucose test strips. Results were compared to blood glucose levels. Correlations between values from the test strips and values from the laboratory were better using the Haemo-Glukotest (r = 0.91) than using the Dextrostix (r = 0.82). As compared to values from the laboratory, however, both glucose test strips gave higher values and did not properly identify all cases of hypoglycemia.

Are polygraphic and cardiopneumographic respiratory patterns useful tools for predicting the risk for sudden infant death syndrome? A 10-year study.

Between 1974 and 1984 we have studied 204 control infants (C) comparing them with 650 SIDS siblings (SS) and 146 near-miss for SIDS (NM). These 1,000 full-term infants were recorded by day polysomnography (DPSG; n = 417), night polysomnography (NPSG; n = 257) and cardiopneumography (CPG; n = 2,600). Records were visually analyzed. In DPSG and NPSG, total amount of central, mixed and obstructive apnea as well as the percentage of periodic breathing was studied in each sleep state (active sleep, AS; quiet sleep, QS; indeterminate sleep, IS, and total sleep, TS) and over the total recording time (TRT). In CPG, only the total amount of central apnea and percentage of periodic breathing over TRT were studied. Infants were grouped according to postnatal age: less than 5, greater than or equal to 5 to less than or equal to 13, and greater than 13 to less than or equal to 26 weeks. In each age group results were compared as follows: C vs. SS, C vs. NM, and SS vs. NM for each parameter studied. Before 5 weeks and after 13 weeks there was no significant difference between C and SS, C and NM, and SS and NM in DPSG and NPSG for all categories of central, mixed and obstructive apnea as well as the percentage of periodic breathing in different sleep states and over TRT. Similar results were obtained in CPG for all categories of central apnea and percentage of periodic breathing over TRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants.

The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer.

[Paroxysmal vagal hypertonia in infants. Apropos of 14 cases]. / Hypertonie vagale paroxystique du nourrisson. A propos de 14 observations.

Fourteen infants presenting with unexplained episodes of weakness or fainting were investigated by repeated Holter monitor recordings and oculocardiac reflexes (OCR). The recordings were then compared with those of 10 normal children in order to try to establish the criteria of vagal hyperreflexia. Results of OCR were collated with those of Holter: there was a good correlation between the length of the cardiac arrest on the OCR and the minimal instantaneous frequency and the maximal change of instantaneous frequency recorded on the Holter. The diagnostic difficulties of these vaso-vagal episodes in infants are emphasized. The potential gravity of these episodes and the possible relation with the sudden infant death syndrome are then discussed in the light of these cases.

Functional residual capacity and sleep states in the premature newborn.

Functional residual capacity (FRC) variations in relation to sleep state changes were studied in 11 premature infants with birth weights of 1.68 +/- 0.48 kg and gestational ages of 32.7 +/- 2.2 weeks (mean +/- SD). Helium dilution was used to measure FRC, and sleep states were identified using neurophysiologic criteria. No significant difference in FRC could be demonstrated between data collected during active sleep (AS) and quiet sleep. However a relationship was shown between AS and paradoxical breathing (p less than 0.02) and between AS and irregular breathing (p less than 0.05). Several factors are discussed which might explain the discrepancy between the present data in premature infants and the previously published data in term infants. (1) Neurophysiologic identification of sleep states does not include breathing pattern whereas behavioral identification does. It is therefore possible that lung volume changes are related to breathing pattern changes and not to sleep state changes per se. (2) Maturational changes may occur among the mechanisms which control FRC, leading to a progressive stabilisation of FRC, the variation of which could become related to sleep state changes.

Sleep apneas in normal neonates and infants during the first 3 months of life.

Sleep polygraphic recording was carried out on 52 normal full-term babies. 16 infants were recorded at 2 - 7 days of age, 14 at 2 to 5 weeks, 13 at 6 to 9 weeks and 9 at 10 - 13 weeks. Central apneas of 2 sec and over were analysed in Active Sleep (AS), Quiet Sleep (QS) and Transitional Sleep (TS). Apnea Index (AI, percent of non-breathing) and Number of Apneas (NA) per 100 min of sleep state (for 2 - 4 sec, greater than or equal to 5 sec, greater than or equal to 6 sec and greater than or equal to 10 sec apneas) were determined. Obstructive and mixed apneas were tabulated separately. % of Periodic Breathing (PB) was also determined. These results were statistically tested using different methods. AI and number of less than 5 sec apneas are higher in AS than in QS during the period studied. A decrease of AI and NA occurs before the end of the 2nd month both in AS and QS. During the first five weeks of postnatal life the AI, the NA and the % of PB are higher in infants born at 38 - 39 weeks of Gestational Age (GA) than in infants born at 40 - 42 weeks. A positive correlation between short apneas (less than 5 sec) and apneas greater than or equal to 5 sec was found in AS and in total sleep. Obstructive and mixed apneas were very infrequent. Apneas are not affected by recording technique, sex or sleeping position of infants. There is a great interindividual variability of NA, particularly during the first month of life. Little normative data has been published so far concerning the incidence of respiratory apneas during day sleep in full-term infants recorded by polygraphy.