Characteristics of sleep apnea syndrome in tetraplegic patients.

OBJECTIVE: To include a larger number of tetraplegics than in previous studies, in order to more reliably characterize the pathogenesis and predisposing factors of sleep apnea in tetraplegia. METHODS: Sleep breathing data and oxymetric values were investigated in 50 randomly selected tetraplegic patients and discussed in context with age, gender, BMI, neck circumference, type and height of lesion, time after injury, spirometric values and medication. A non-validated short questionnaire on daytime complaints was added. RESULTS: Thirty-one patients out of 50 had an RDI > or =15, defined as sleep disordered breathing (SDB); 24 of them combined with an apnea index of 5 or more, these cases were diagnosed as sleep apnea syndrome (SAS). SAS was apparent in 55% and 20% of the studied men and women, respectively. Regression analyses showed no significant correlation between RDI and lesion level, ASIA impairment scale or spirometric values. In contrast, a significant correlation between RDI and age, BMI, neck circumference and time after injury could be shown. Kruskal-Wallis test for dichotomous non-parametric factors, such as gender, cardiac medication and daytime complaints, showed significant differences with regard to RDI. In contrast to able-bodied people with SAS, daytime complaints were only present in tetraplegic patients with severe pathology (RDI>40). CONCLUSION: Incidence of SAS is high in tetraplegia, particularly in older male patients with large neck circumference, long standing spinal cord injury and under cardiac medication. As tetraplegics with RDI between 15 and 40 reported no daytime complaints and often have normal BMI, these tetraplegics are not clinically suspicious for SAS. The increased use of cardiac medication in tetraplegics with SAS may implicate a link between SAS and cardiovascular morbidity, one of the leading causes of death in tetraplegia.

Spectral power and coherence analysis of sleep EEG in AIDS patients: decrease in interhemispheric coherence.

Fifteen patients aged between 26 and 55 years with the acquired immunodeficiency syndrome (AIDS) and various cerebral manifestations of the disease underwent an all-night sleep electroencephalogram (EEG) registration. The recordings of 15 age-matched volunteers were examined as controls. Sleep stages were determined visually and the following spectral analysis was based on corresponding artifact-free 40-second periods. The sampling rate was 64 second-1, the spectral resolution was 0.25 Hz and the frequency ranged from 0.25-24 Hz. The power density spectra of eight EEG derivations (left and right frontopolar, frontal, central and occipital; reference montage to the ipsilateral Cb electrodes) and the coherence spectra of interhemispheric (interfrontal, interoccipital) and intrahemispheric (frontooccipital, left and right) channel pairs were computed. The power density of the patients in the 11.5-13-Hz frequency range of nonrapid eye movement (NREM) sleep was considerably lower than that of the controls (p < 0.05 and p < 0.01 at left and right frontal derivations, two-tailed Mann-Whitney U test). The power density of rapid eye movement (REM) sleep showed no consistent differences between the two groups. The interfrontal coherence of the whole frequency range below 12 Hz was markedly lower in the patient group. This applied to NREM sleep and also to REM sleep (p < 0.01 and p < 0.001 for different frequency bands between 1 and 12 Hz in NREM and REM sleep). Possible relations to clinical features are discussed.

[Pattern recognition techniques in sleep polygraphy]. / Verfahren zur Mustererkennung in der Schlaf-Polygraphie.

The evaluation of EEG-patterns is usually accomplished by visual analysis. Nowadays however, even personal computers are fast enough for an efficient pattern recognition of EEG signals. Using sleep spindles and K-complexes as examples, our aim was to demonstrate how patterns can be detected in an EEG signal with a high degree of accuracy. Furthermore, recognition of K-complexes has been improved by applying an additional "adaptive algorithm" allowing individual adjustments to the signal's form and amplitude.

Short-term sleep EEG recordings after partial sleep deprivation as a routine procedure in order to uncover epileptic phenomena: an evaluation of 719 EEG recordings.

All night sleep deprivation prior to an EEG registration causes some inconvenience not only to the organization of the EEG department but presents a burden on the patients as well as their family members, and for these reasons is not suitable to be frequently employed as a routine procedure. As an alternative, we performed short-term sleep recordings in the early afternoon following a partial sleep deprivation of the patients during the preceding night. This method was well accepted by the patients and their family. Our only goal was to shorten the total time of night sleep using the following guideline: for very small children 22.00-06.00; for 4-14-year-old patients 24.00-06.00; and for patients older than that 01.00-06.00. 79.9%, out of 719 patients (573) who had been given the above instructions subsequently showed sleep patterns in their EEG. Additionally we had to administer an oral dose of promazine to only 67 patients. However, for the most part, patients showed only light sleep stages: 114 patients only reached sleep stage 1; 323 patients sleep stage 2; 88 patients sleep stage 3; and 48 patients sleep stage 4. As expected, REM sleep was never recorded. Nonetheless, in 32 out of 146 patients who were tired but unable to fall asleep, epileptic patterns could be provoked. In 636 patients, the EEG-recording after sleep reduction was ordered because of a suspected seizure disorder; in the remaining patients it was initiated solely because of sharp components in the routine-EEG. In 341 (53.6%) of the patients with suspected epilepsy, electroencephalographic activity indicative of a seizure disorder was activated. Such epileptic patterns were recorded almost exclusively in stages of waking, 1 and 2. Only in one out of the 124 patients who reached sleep stages 3 and 4 epileptic patterns were not seen until deep sleep was entered. We observed 2/s, 3/s and 6/s spike-and-wave complexes, sharp waves, spikes, polyspikes, groups containing remarkably sharp components and so called sharp vertex grapho-elements. Patients with suspected seizure disorders frequently show grapho-elements which can be interpreted as the expression of a disposition for epilepsy. These sharp vertex elements were evident in 54 out of 719 short term sleep recordings, more often in children than in adults. 49 times they coincided with typical epileptic discharges such as sharp waves, spikes or spike-and-waves in the same recording.

Periodicity analysis of sleep EEG in the second and minute ranges--example of application in different alpha activities in sleep.

To investigate the temporal organization of EEG sleep activity in the second and minute ranges we developed a method which, based on Fourier transformation, allows the presentation of periodic oscillations of spectral power and coherence. The application of this method is demonstrated in 3 subjects with different types of alpha activity during sleep: (a) alpha-sleep pattern (a physiological variant of NREM sleep activity); (b) abnormally increased arousal alpha activity. The results show that differences in the temporal organization of these alpha activities can be determined with the following parameters: period length, duration of sequences with periodic activity, number and rate of these sequences, and proportion of periodicities generated simultaneously in the left and right hemispheres. The physiologically modulated periodicities of the alpha-sleep pattern are contrary to a stereotyped 40-60 sec periodicity of abnormal arousal alpha activity. Such abnormal periodicity corresponds to periodicities occurring in association with other sleep disturbances, such as sleep apnea or periodic movements in sleep. Periodicity analysis gives additional criteria for a more refined evaluation of normal as well as abnormal sleep structure.

EEG sleep activities react topographically different to GABAergic sleep modulation by flunitrazepam: relationship to regional distribution of benzodiazepine receptor subtypes?

Spectral analysis was performed to study the response of various EEG sleep activities to a modification of GABAergic sleep regulation by flunitrazepam. We observed sleep stage- and sleep cycle-dependent differences in the topographic distribution of the reactions. An increase in power density was found in the frontal regions for the alpha 2 and sigma 1 frequency band whereas a decrease in power density was emphasized in the posterior regions for the delta and alpha 1 frequency band. These topographic differences might be related to the regional distribution of benzodiazepine receptor subtypes.

[Polygraphic sleep data in AIDS patients]. / Schlafpolygraphische Daten von AIDS-Patienten.

Somnopolygraphic recordings were registered from 29 patients with AIDS, their age ranged from 20 to 55 years (mean: 40.9; median: 44). The patients represent the full range of cerebral disintegration representing the picture of a progressing destruction of physiological sleep organization. Some disturbances begin quite early and progress successively, such as the reduction of REM- and delta-sleep as well as the reduction of sleep spindle- and K-complex-densities. Other changes are not manifest until intellectual capabilities break down; they occur massively such as the shortening of real sleep time and the reduction of sleep stage 2 with a simultaneous increase in waking time. It is remarkable that despite the enormous REM reduction there is no suppression of REM periods corresponding to "REM sine REM". REM periods become very short at an early stage; this is not only because the patients awake more frequently and earlier from their dream periods.

[A system for continuous digitizing and evaluation of 32 biosignals from all-night sleep leads]. / System zur kontinuierlichen Digitalisierung und Auswertung von 32 Biosignalen bei Ganznacht-Schlafableitungen.

In all-night sleep recordings usually 12 to 16 channel electroencephalographs are used to record the electrical activity of the brain. A detailed analysis of EEG sleep activity, however, requires the inclusion of at least 19 electrodes placed according to the international 10-20 system in order to compare the variations of the activities in different brain areas. In addition polygraphic parameters such as ECG, respiration and actogram, to mention just a few, have to be recorded depending on the type of study. Therefore the number of recording channels has to be increased for a complete polygraphic investigation. We developed a 32 channel unit with a personal computer and corresponding hardware interfaces allowing the continuous digitalization of up to 32 bioelectrical signals throughout the whole night (8 hours). The recorded data can be presented graphically and evaluated according to the usual methods such as power spectrum, coherence and periodicity analysis. Additionally the use of algorithms for pattern detection permits automatic analysis of EEG segments regarding particular sleep patterns e.g. sleep spindles and K-complexes.

[The effect of age on sleep spindle and K complex density]. / Der Einfluss des Alters auf die Schlafspindel-und K-Komplex-Dichte.

The amount of sleep spindles and K-complexes shows a great interindividual variety of combinations, such as many or few sleep spindles and K-complexes respectively. There seems to be no direct correlation between the amount of sleep spindles and K-complexes intraindividually. In our unselected population - age range between 18 and 77 years - the mean sleep spindle density is at 2.59 +/- 1.85/min and the mean K-complex density at 1.96 +/- .96/min stage 2. The diffuse individual distribution, however, does not reflect the age factor involved. The sleep spindle and K-complex density were practically half the amount for the age group above 50 years as compared to the age group of less than 30 years.

Detection of brainstem lesions in multiple sclerosis: comparison of brainstem auditory evoked potentials with nuclear magnetic resonance imaging.

Topographical information provided by brainstem auditory evoked potentials (BAEPs) was investigated in 43 patients by comparison with cerebral nuclear magnetic resonance imaging (NMR). Lesions in the region of the brainstem auditory pathways were demonstrated by BAEPs in 44.2%, and in 39.5% by NMR. As regards brainstem levels, in 15/21 (71.4%) with abnormal findings at least one lesion was verified by NMR-matched BAEP results. The study confirms the topographical information provided by the BAEPs on the different levels of the brainstem, but not the assumption that generation of the BAEPs is predominantly ipsilateral. BAEPs retain their importance for the detection of disseminated lesions in the diagnosis of multiple sclerosis (MS) in the era of expensive imaging methods.

[Effect of lormetazepam, triazolam and flunitrazepam on rapid eye movements, K-complexes and sleep spindles in normal probands]. / Der Einfluss von Lormetazepam, Triazolam und Flunitrazepam auf die schnellen Augenbewegungen, K-Komplexe und Schlafspindeln gesunder Probanden.

"Equipotential" doses of lormetazepam, triazolam and flunitrazepam were tested regarding their influence on K-complexes, sleep spindles and rapid eye movements. The receptor affinity was used to determine the equipotency. In this respect triazolam, lormetazepam and flunitrazepam show a relationship of 1:2:4. Lormetazepam, however, showed only slight changes of the three neurophysiological parameters even when given as double dosage. Triazolam and flunitrazepam reduce K-complexes considerably, increase sleep spindles enormously and reduce REM activity markedly; both substances suppress the first REM period, flunitrazepam even the second one. All three of the benzodiazepines have the same effect on the dissociation of K-complexes and sleep spindles; epochs with K-complexes or sleep spindles are favored compared to epochs with K-complexes and sleep spindles. The general reduction of K-complexes and the increase in sleep spindles can be interpreted as a sleep protective function. When deciding on the dosage, however, REM-suppression should be used as a guide since it has the strongest effect on the cyclic structure of sleep which nowadays is considered to be the safest evidence of well balanced sleep behavior.

Anticonvulsant effect of clonazepam in the dog: development of tolerance and physical dependence.

Dogs were treated with clonazepam, 0.5 mg/kg orally, b.i.d., for 3-6 weeks. The development of tolerance to the anticonvulsant effect was followed by weekly determinations of the convulsive threshold by infusion of pentetrazole, 10 min after i.v. injection of 0.1 mg/kg clonazepam. In all 6 dogs tolerance was apparent after 1-2 weeks of treatment; in 1 dog the anticonvulsant effect had been totally lost after 3 weeks of treatment. Tolerance is regarded to be "functional" since the elimination half-life of clonazepam increased considerably with the duration of the treatment. One day after withdrawal of clonazepam the convulsive threshold had fallen below the control value in all dogs, but 1 week later it had recovered to the control level. Other signs of physical dependence after withdrawal were hyperthermia in 2 dogs as well as anorexia with weight loss in 5 out of the 6 dogs. In anesthetized dogs, relaxed by suxamethonium and ventilated, the effect of repeated injections of clonazepam on the EEG spiking activity maintained by an infusion of pentetrazole was studied; there was no indication for the development of acute tolerance.

Development of tolerance to the anticonvulsant effect of diazepam in dogs.

In dogs the development of tolerance to the anticonvulsant effect of diazepam was followed by weekly determinations of the convulsive threshold for pentetrazole, 10-15 min after intravenous (i.v.) injection of 0.25 or 0.5 mg/kg diazepam. As soon as after 1 week of oral treatment with diazepam, 0.25 or 0.5 mg/kg three times daily (t.i.d.), the pentetrazole threshold showed a decline or even a fall to the control level in spite of unaltered or rising concentrations of diazepam and its active metabolites. Tolerance also developed when the dogs were treated with chlorazepate, 2 mg/kg t.i.d., between the weekly diazepam injections for threshold determination. The results favor a functional type of tolerance since there was no indication of a more rapid inactivation of diazepam. Treatment with desmethyldiazepam (2 mg/kg i.v. for threshold determination and oral treatment with the desmethyldiazepam precursor chlorazepate, 2 mg/kg t.i.d.) did not produce tolerance. In further experiments in dogs anesthetized, relaxed with suxamethonium and ventilated, a spike-wave activity in the EEG was induced and maintained by an injection and subsequent infusion of pentetrazole. Out of 6 dogs, receiving 4-5 i.v. injections of 0.25-0.5 mg/kg diazepam, 2 showed the phenomenon of acute tolerance, i.e. the effect of the drug on the spiking activity in the EEG became less from one injection to the next, and thus paralleled a situation which may be observed during treatment of clinical status epilepticus. No acute tolerance was observed in corresponding experiments with desmethyldiazepam.

[Clinical significance of increased reaction to photostimulation in the alpha frequency range]. / Zur klinischen Bedeutung der gesteigerten Photostimulationsreaktion im alpha-Frequenzbereich.

When evaluating responses in the EEG to intermittent photic stimulation usually the emphasis is placed on the differentiation of photoparoxysmal and photomyogenic responses as well as asymmetric driving effects such as locally increased activation of slow frequencies or locally reduced activation of the basic rhythm indicating a focal disturbance. Apart from these responses, however, sometimes an increased rhythmic response within the alpha-frequency range can be observed. This response is characterized by a bilateral, unproportionately strong activation or increase in amplitude of the particular rhythm, as well as a growing synchronized activation of beta-waves. There is, however, no evidence of paroxysmal characteristics neither directly by spike components, nor indirectly by spread to other regions of the brain. The occurrence of this pattern is studied in a mixed clinical population of 3110 patients whose EEGs included photic stimulation as a routine activating procedure. The described response occurred in 1.4% with a remarkable predominance in female patients. Particularly middle and higher age groups were represented. There were significant differences in age, sex and types of illness compared to other in-patient groups as well as a matched control group with a similarly unremarkable resting activity in the EEG, but without the increased response to photic stimulation. In the young age group traumatic or inflammatory diseases prevailed, in middle and higher age groups cerebrovascular disturbances, vasomotor headaches or migraine and peripheral vascular diseases, e.g. with coronary manifestation. The symptoms include a high proportion of vegetative regulatory dysfunctions and neurasthenic-depressive complaints. There is no obvious relationship to disturbances of the occipital lobes or to seizure disorders whereas regarding not only the symptomatology but also the characteristics of the resting activity in the EEG there are definite relationships to vertebrobasilar insufficiency. Experimental findings and clinical observations support the assumption that a functional alteration located in subcortical, mesodiencephalic areas is the condition responsible for the increased rhythmic response to photic stimulation, however without a specific etiologic significance. Based on neurophysiological models regarding the regulation of thalamo-cortical rhythmicity one can consider a disturbance of mesodiencephalic reticular systems as the mechanism responsible for a shift in the regulation of synchronization-desynchronization-levels with a desinhibitory effect. This leads to the conclusion that not only a unilateral but also a bilateral increase in the response to photic stimulation has to be taken into account as an indicator of a functional alteration. Such an indicator can be particularly valuable when there are only mild symptoms of an apparently unspecific nature.

The alpha-sleep pattern. Differentiation from other sleep patterns and effect of hypnotics.

We observed the alpha-sleep pattern in 6 out of 44 subjects who offered neither somatic nor psychological complaints. All of the 6 subjects demonstrated the pattern consistently over a period of several years. 14 of the polygraphic sleep EEGs were recorded when free of any drugs, 10 after administration of benzodiazepine hypnotics. The alpha-sleep pattern is superimposed on all the regular patterns during any of the different sleep stages, and shows a cyclic representation with an increase correlating to the delta-sleep stages 3 and 4. It can be differentiated from other activities due to its localization, frequency characteristics, occurrence in relation to different sleep stages, and modification under the influence of benzodiazepine hypnotics. In contrast to the sigma-spindle activity, the alpha-sleep pattern is reduced with these drugs. Regarding the functional significance of the alpha-sleep pattern one might consider the possibility that it indicates a partially heightened level of sleep depth.

[Comments on the rules by Rechtschaffen and Kales about the visual scoring of sleep EEG recordings]. / Kritische Bemerkungen zu den Regeln von Rechtschaffen und Kales über die visuelle Auswertung von EEG-Schlafableitungen.

The rules by Rechtschaffen and Kales present numerous problems; they sometimes even contradict physiological facts. This is due on the one hand to the manual being limited to central leads only, and on the other hand to rules which are partly too narrow, partly too broad and partly too complex. Furthermore, there are situations and physiological facts for which the manual does not have any rules. The exclusive evaluation of central leads has to result in a different scoring for numerous epoches of stages than an evaluation of leads from all hemisphere electrodes. In addition, frontal or occipital graphoelements such as mitten-pattern and sleep lambda are not even included. It is often difficult to make a distinction between an "alpha-sleep type" and pre-arousals (micro-arousals); the latter also applies to alpha groups in REM sleep. In particular however, if frontal, parietal and occipital leads are included, then the stage 2, above all however stages 3 and 4 will be represented more frequently, as sigma spindles, K-complexes and delta-waves are frequently found in a recognizable form only in the non-central leads. Further difficulties result from different paper speeds of 15 or 10 mm/s and from the rule concerning the allocation from stage 1 to stages 2 or REM.

[A contribution to the psychophysiology of infantile dysmegalopsy (author's transl)]. / Zur psychophysiologie der infantilen Dysmegalopsie.

A 9 year old boy was able to evoke microptic experiences voluntarily. Clinical and historical signs of minimal brain dysfunction were present. An epileptic etiology could neither be proven nor ruled out. Synchronized EEG- and Video recording allowed us to analyze the EEG and the corresponding behavior by using sequential spectral analysis of the EEG data. Coinciding with a progressive increase in rhythmic 6-7 cps. activity we observed a behavior which appeared to correspond to a state of narrowed attention. He signalized the onset of a micropsy a few seconds after the transition from this pattern into one which showed a relative voltage decrease and the reappearance of some alpha-activity. The end was signalized by him coinciding with the recurrence of normal waking activity. Our findings--like those of others--suggest that the gradual development of hypnagogic phenomena is bound to a state of lowered vigilance. The reappearance of alpha activity and the voltage decrease seem to represent an unstable intermediary state with partial arousal preceding the restitution of normal wakefulness. Since the onset of the micropsy was signalized only after manifestation of the intermediary EEG-state, we conclude that partial arousal is a prerequisite for giving an indication of hypnagogic experiences in a quasi retrospective manner.