Sleep alterations in juvenile neuronal ceroid-lipofuscinosis.

In juvenile neuronal ceroid-lipofuscinosis (JNCL), sleep disorders are common. The purpose of this study was to investigate the sleep structure of 28 patients with JNCL compared with healthy controls subjects and to clarify the pathophysiology underlying the sleep disturbances in these patients. Each of 28 patients with JNCL (age range = 6-27 years), with or without sleep complaints, underwent one night of polysomnography. Electroencephalographic, electro-oculographic, electromyographic, and electrocardiographic findings were recorded. Sleep was scored and analyzed visually. The sleep parameters of the patients were compared with those of healthy control subjects. In most of the patients, the total sleep time, sleep efficiency, and percentages of rapid eye movement (REM) and non-REM (NREM) stage 2 sleep were significantly decreased, and the percentages of NREM stage 1 and slow-wave sleep and the number of nocturnal awakenings significantly increased. The percentage of NREM stage 1 and the number of awakenings increased with age and clinical stage. Paroxysmal epileptiform activity during light sleep (NREM stages 1-2) and high-amplitude delta-wave activity with intermingled sharp waves during slow-wave sleep were characteristic of the recordings. The present study revealed that in patients with JNCL, sleep is consistently altered.

Circadian rhythm studies in neuronal ceroid-lipofuscinosis (NCL).

Sleep disorders are common in NCL patients. The patients have problems such as frequent awakenings, difficulties with sleep onset, nightmares, and night terrors. The aim of the study was to examine whether the sleep disturbance in NCL can be explained on the basis of desynchronised circadian rhythms. Therefore we studied diurnal patterns of melatonin, cortisol, body temperature, and motor activity of 14 patients. The group consisted of 8 JNCL patients, 5 INCL children, and one boy with Jansky-Bielschowsky disease of the variant type. There were healthy age- and sex-matched control subjects. The blood samples for serum melatonin and cortisol were collected every 2 hours during 24-hour periods. Body temperature was recorded continuously for a 24-hour period by a polygraph. Diurnal motor activity was measured by wrist actigraphy for 5 days. In most of our patients sleep was fragmented and the sleep phase was irregular. Disturbances in the daily hormonal rhythms occurred only in the minority of the patients and only at an advanced stage of the disease. Although disturbances in the body temperature rhythm were found in about half of the patients, a general failure in the circadian regulatory system does not explain the frequent disturbances of the sleep-wake cycle of the NCL patients.

Effects of a cognitive-behavioural weight loss programme on overweight obstructive sleep apnoea patients.

Thirty-two obese patients (Body Mass Index (BMI) = 38.5 +/- 3.7) with obstructive sleep apnoea (the average number of oxygen desaturations per hour of sleep exceeding 4% from the baseline (ODI4) = 38.64 +/- 23.9) underwent a one-year cognitive-behavioural weight reduction programme with a one year follow-up period. The criteria for successful treatment were (i) a decrease in ODI4 to less than 10 and (ii) a decrease in ODI4 that was greater than 50%. Fourteen (44%) patients were considered to be treated successfully at six months. When the patients were grouped according to weight loss 23 patients had lost more than 5 kg; 12 (52%) of them belonged to the group treated successfully. At 24 months, however, only three (9%) patients could be regarded as treated successfully and six patients had been transferred to other treatment modes (Nasal Continuous Positive Airway Pressure (nCPAP) and uvulopalatopharyngoplasty (UPPP)). The changes in weight correlated with the changes in ODI4 (r = 0.47 and 0.63 at the 6-month and the 24-month evaluation, respectively).

Snoring and cardiovascular risk factors.

The association of snoring with some cardiovascular risk factors was studied cross-sectionally by a postal survey among 3750 males aged 40-59 years. In univariate analyses, snoring associated statistically significantly (P < 0.01) with hypertension, smoking, obesity, heavy alcohol use, physical inactivity, dyspnoea, hostility and morning tiredness. In a multiple logistic regression model adjusted by age, snoring associated significantly with smoking, obesity, physical inactivity, hostility and morning tiredness. When smoking was excluded from the multivariate model, alcohol use was also associated significantly with snoring. The association of snoring with smoking, and with obesity seemed to be almost independent from other studied correlates of snoring. Our results indicate that in further studies on predictive value of snoring with regard to coronary heart disease and stroke, the associations of snoring with hypertension, smoking, obesity, heavy alcohol use, physical inactivity and hostility have to be considered, as these risk characteristics may cause confounding effects.

Evaluation of Sleep Expert--a computer-aided decision support system for sleep disorders.

Sleep Expert--a medical decision support system--is a prototype program, with knowledge based on the International Classification of Sleep Disorders (1990). The goal of this project was to evaluate Sleep Expert. In the evaluation project the knowledge of the program was first validated. Three physicians, experts in sleep disorders, were asked to choose 10 typical patient cases with sleep disorders, and to write a description. They also made a diagnosis for each case. Next, each expert made a diagnosis of the cases supplied by the other experts. They were not given the original diagnosis. The 'right diagnosis' (so-called majority agreement) was determined from the three diagnoses. Then the diagnosis of each expert was compared with the 'right diagnosis'. Two physicians, not experts in sleep disorders, were asked to make a diagnosis by using Sleep Expert. Compared to the 'right diagnosis' the diagnoses of each user (non-expert physician) were correct to 63 and 70% of cases, which is quite a good result, although it does not reach the level of the expert physicians (> or = 87%). The functionality of Sleep Expert was studied by using a limited inquiry. On the basis of the user inquiry Sleep Expert provided a useful clinical tool for non-experts.

Epidemiology of obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is the most common organic disorder of excessive daytime somnolence. In cross-sectional studies the minimum prevalence of OSAS among adult men is about one per cent. Prevalence is highest among men aged 40-65 years. The highest figures for this age group indicate that their prevalence of clinically significant OSAS may be 8.5% or higher. Habitual snoring is the most common symptom of OSAS (70-95%). The most significant risk factor for OSAS is obesity, especially upper body obesity. Other risk factors for snoring, and for OSAS, are male gender, age between 40 and 65 years, cigarette smoking, use of alcohol, and poor physical fitness. Upper airway obstruction with snoring or sleep apnea are commonly seen in children of all ages. Snoring is very common among infants and children with Pierre Robin syndrome and among infants with nasal obstruction. Snoring and obstructive sleep apnea are also very common in men with acromegaly. Many other syndromes or diseases exist in which the upper airway is narrowed. Prevalence of snoring and sleep apnea is increased in all such situations. It has been suggested that sleep apnea may be one mechanism contributing to sleep-related mortality. The prevalence of every night snoring seems to decrease after the age of 65. However, more than 25% of persons over 65 have more than five apneas per hour of sleep. It remains to be seen whether this finding has clinical significance. Partial upper airway obstruction, even without apneas, may influence pulmonary arterial pressure and may cause daytime sleepiness and some health consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome in subjects with alcohol-provoked seizures.

The outcome in 165 subjects with either an unknown (n = 93) or an alcohol-related (n = 72) seizure etiology, admitted to the emergency room of a general hospital in 1977-1978, was assessed after 10 years on the basis of subsequent hospital records and death-certificate-based mortality data. Alcohol and/or drug poisoning was the most frequent cause of death in the group with alcohol-related seizures. Sixty-four percent of the deaths in this group were directly related to alcohol abuse. The crude mortality was 45.8 (expected 8.6)/100 persons/10 years in the group with alcohol-related seizures and 15.1 (expected 6.0)/100 persons/10 years in the other group, the odds ratio between the groups being 4.8. Twenty percent of those with an unknown seizure etiology were found to show alcohol-related seizures, while the seizure etiology remained unknown in 59%, and a specific etiology other than alcohol abuse was revealed in 21% during the follow-up period. We conclude that alcohol abuse is an important, though often undetected, seizure etiology carrying a poor prognosis. The difference in mortality between the groups was due more to alcoholism than to seizures. There was no difference in mortality between those with a first alcohol-related seizure and those with previous alcohol-related seizures.

Atrial natriuretic peptide in habitual snorers.

We studied nocturnal and early morning variations in the concentration of plasma atrial natriuretic peptide (ANP) in 17 men who habitually snored. The subjects had a mean age of 51.0 +/- 5.8 years, range 41-62 y with a mean body mass index (BMI) of 32.9 +/- 7.3 kg/m2. The concentration of plasma ANP was measured by radioimmunoassay of venous samples at 10 p.m., midnight, 6 p.m. and 8 p.m. All night sleep recordings were conducted with the static charge sensitive bed to monitor body and breathing movements and a BIOX III Pulse Oximeter for the blood oxygen saturation level. Nine patients were defined as having the obstructive sleep apnea syndrome (OSAS). No significant diurnal variation for ANP concentrations was detected. At 8 a.m. five OSAS patients and two others had ANP concentrations above normal (70 pg/ml). Neither mean oxygen saturation during the night nor arterial hypertension discriminated between the high and low ANP groups at 8 a.m. The best discriminators for a high concentration of ANP at 8 p.m. were marked obesity (BMI greater than or equal to 30 kg/m2), over 400 movements lasting less than five seconds, and over 30% of active sleep per night. In a multivariate regression analysis age, percentage of active sleep during the night, BMI and the median oxygen saturation level during the night explained 76.4% of the total variance of ANP at 8 a.m. In a similar analysis the median oxygen saturation level during the night and BMI both explained the variance of ANP significantly. The whole model explained 53.7% of the variance of the ANP concentrations at 6 a.m.(ABSTRACT TRUNCATED AT 250 WORDS)

Are syntax errors due to the amino acid sequence of neuroleukin involved in the pathogenesis of the acquired immunodeficiency syndrome (AIDS) and insulin dependent diabetes mellitus (IDDM)?

The main principles of this hypothesis are very general: (i) signal-detection from background noise is one central issue in electronics; (ii) an important source of misunderstanding at different levels of communication is the fact that a given signal may have different meanings in different contexts; (iii) the unique role of chance in developmental biology is generally appreciated (37). In AIDS the basic defect would be the human specific inability to distinguish between the amino acid sequence of neuroleukin and peptides derived from the gp120 envelope protein of HIV, resulting in a slowly progressing failure of the CD4+ T cell-mediated immunity. In IDDM the postulated HLA class II-dependent hypersensitivity to immunological noise could predispose to random contacts between cells with a different signalling language. In the ensuing dialogue neuroleukin secreted by T cells would imply a continuous demand for insulin secretion to pancreatic beta cells resulting in diabetes. This hypothesis does not contradict with the provocative ideas proposed by Duesberg concerning the relationships between HIV and AIDS (24) and the known data on the genesis of IDDM.

Evaluation of automatic analysis of SCSB, airflow and oxygen saturation signals in patients with sleep related apneas.

We have developed a computerized analysis of respiratory and body movements (static charge sensitive bed [SCSB]), oxygen saturation (pulse oximeter), and airflow (thermistor) for the evaluation of sleep related apneas. The cumulative distribution of oxygen saturation, the number and distribution of desaturation events, and the duration and type of apneas are assessed. Analysis is performed separately during the total recording time and during the time when the patient sleeps on his back. We have compared the automatic analysis with the results obtained on simultaneous daytime polysomnograph naps in 55 subjects (snorers or obstructive sleep apnea syndrome [OSAS] patients). The compressed graphs obtained automatically demonstrated a periodic breathing pattern in all 22 patients who presented sleep-related apneas at polygraphic recording. The cumulative distribution of oxygen saturation was not as steep in the apnea patients as in patients not showing apneas; in 19 of the 22 OSAS patients, the value was outside our normal limits (80 percent of the recording time inside 3.6 percent SaO2 variation band). The apnea index (AI) was 26.4 in manual and 23.3 in automatic analysis. Using the automatic method there were three false negative cases in the analysis of desaturations; in these patients periodic breathing was present in output graphs indicating need for further polygraphic assessment. The duration of apneas in the automatic analysis was shorter than in manual analysis, but the agreement was sufficient for screening purposes (mean error less than 3 s, mean duration of apneas 20.1 s). The automatic method is presently used in clinical routine for screening purposes, for assessment of the severity of the disorder and the type of treatment that a subject may need, in epidemiologic investigation and follow-up of the treatment.

Urinary catecholamines in habitual snorers and controls.

Habitually snoring men (n = 10, mean age 47.3 years, range 44-52 y) were compared with non-snoring controls (n = 11, mean age 46 y, range 41-52 y). The mean body mass index of the groups did not differ significantly and only 2 of the subjects were grossly obese. Whole-night sleep recordings with recording of body-and-breathing movements and the peripheral blood oxygen saturation were made. The 12-h urinary specimens were collected from 6.30 p.m. to 6.30 a.m. and analysed for epinephrine, norepinephrine and dopamine, respectively by liquid chromatography with electrochemical detection. The mean diastolic blood pressure level of the habitual snorers was significantly higher than that of the non-snoring controls (P less than 0.05). An association was seen between snoring and diastolic blood pressure in individuals with normal weight but not in the obese. However, no significant group differences in any of the measured catecholamine levels were found.

Influence of improved drinking habits on brain atrophy and cognitive performance in alcoholic patients: a 5-year follow-up study.

In the period 1977-1979, a sample of consecutively admitted alcoholic in-patients was studied with CT scan of the brain and neuropsychological tests. A subsample of 52 patients met the following criteria: age less than 46 years, no history of severe head injury or focal signs of traumatic brain damage, and no history of liver disease, drug abuse, or long-lasting anticonvulsant therapy. However, 72% of the patients showed brain atrophy and 49% intellectual impairment as compared to 16% and 13%, respectively, in an age-matched sample of men from the general population. Five years later, after excluding patients with head trauma, serious alcoholic liver disease and drug abuse, 37 patients were reinvestigated. Sixteen patients were abstinent or had greatly improved drinking habits during the 5-year follow-up period and 21 were still drinking. Alcohol abstinence was found to be associated with a regress of cortical atrophy and central atrophy as assessed by the width of the 3rd ventricle. However, the recovery was not complete as compared with the prevalence of atrophy in the sample from the general population. Among the patients a significant improvement in one cognitive test and a trend to improvement in some other tests associated with improved drinking habits was observed. Regression of central atrophy as assessed by a decreased diameter of the 3rd ventricle was associated with improvement in the very same cognitive tests. The results suggest that both atrophy of the brain and cognitive ability can improve in alcoholics who give up drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive function in middle-aged snorers and controls: role of excessive daytime somnolence and sleep-related hypoxic events.

Association of snoring and cognitive function was studied in 46 habitually snoring men ages 41-52 years, and 60 occasionally or never-snoring control male subjects of the same age group. Sleep recordings with monitoring of apneas and hypopneas were made with the static-charge sensitive bed method. Blood oxygen saturation was measured with an oximeter and the snoring sounds were recorded with a microphone after clinical and neuropsychological assessment. A questionnaire with items on excessive daytime somnolence (EDS), sleep, and snoring quality was also used. EDS (as measured by items on the questionnaire) associated with tests requiring concentration, memory retention, and verbal and spatial skills in the habitual snorers group. The number of oxygen desaturation episodes exceeding 4% associated with defective delayed Recall of Logical Stories of the Wechsler Memory Scale and with spatial orientation (Clock test) in the habitual snorers' group even after adjusting for age and obesity.

Sleep apnea in multiinfarct dementia and Alzheimer's disease.

Sleep-related hypopneas and apneas were studied in 19 patients with multiinfarct dementia (MID), in 21 patients with Alzheimer's disease (AD), and in 26 healthy control subjects using the Static Charge-Sensitive Bed (SCSB) method. Demented patients had more apneas or hypopneas and more disturbed sleep than the control subjects. Over 10 apneas/hypopneas per hour of sleep were detected in 47.5% of the demented patients and in 19.2% of the control subjects (p less than 0.05). Restlessness comprised 46.7% of the time in bed in patients with AD and 49.6% in those with MID, but only 102.% in the control subjects (p less than 0.001, controls versus demented). The total duration of apneas and hypopneas calculated from the total sleeping time was greater than 10% in 60.0% of the demented patients and in 15.4% of the control subjects (p less than 0.001). Patients with MID tended to have more apneas/hypopneas than those with AD, and apneas/hypopneas tended to increase in direct proportion to the severity of dementia. Age had no effect on the proportion of apneas and hypopneas among demented patients or control subjects, but male controls had more apneas and hypopneas than did female controls.

Periodic breathing and hypoxia in snorers and controls: validation of snoring history and association with blood pressure and obesity.

Fifty-two men (aged 41-50 years) of whom 25 reported habitual and 27 of occasional or never snoring were examined clinically. Whole-night sleep recordings of body and breathing movements, snoring and blood oxygen saturation were made. Hypoxic events exceeding 4% from the baseline were counted. Ninety-three percent of those classified snorers by the recordings were habitual or occasional snorers, but 50% of those similarly classified non-snorers had reported habitual or occasional snoring. Four habitual snorers had abnormal breathing indices and polysomnography established obstructive sleep apnea syndrome (OSAS) in one. Thus, self-reported habitual snoring is a reliable OSAS-screening method. Estimated prevalence of OSAS based on this study is 0.4-1.4%. In multivariate regression analysis, the hypoxic events were explained by obesity and apneic events. The diastolic blood pressure level was best explained by obesity, but not hypoxic or apneic events or snoring history.