[Central nervous system activation in opioid dependent patients, evaluation with Fourier analysis of pupillary oscillations]. / Zentralnervöse Aktiviertheit bei opioidabhängigen Patienten, evaluiert durch Fourieranalyse der Pupillenoszillationen.

The aim of the present investigation was to determine whether Fourier analysis of pupillary oscillations permits detection of differences in the activation of the central nervous system of opioid-addicted patients. We analysed pupillary oscillations during the recording period of static pupillometry, which lasted 25.6 s. Using Fourier analysis, the spectrum was divided into five frequency bands (0.0-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80, 0.81-1.0 Hz); the total spectrum (0-1 Hz) was also assessed. Three groups of patients were selected: the group addicted to heroin (consuming exclusively heroin) consisted of 26 patients with a mean age of 25.0 +/- 6.3 years, the methadone substitution group of 20 patients with a mean age of 30.9 +/- 8.2 years, and the morphine substitution group of 20 patients with a mean age of 33.2 +/- 4.6 years. The 3 patient groups were compared with normal controls of similar age (25.1 +/- 4.6 years). In the frequency band of 0.0-0.20 Hz the morphine group showed significantly lower amplitudes than the heroin group. Also in the frequency band of 0.41-0.60 Hz the morphine group differed significantly from the other groups concerning lower amplitudes, reflecting deactivation. In the total spectrum of 0 to 1 Hz the differences between these two groups were significant. Comparison with normal controls also showed significant differences. The groups were further divided according to dose (high/low): Patients of the heroin group as well as those of the methadone and morphine groups who had consumed higher doses showed greater activation of the central nervous system. In conclusion the morphine group was more deactivated than the methadone and heroin group and patients who received higher doses of the substances showed greater central nervous activation. Thus, the measurement of central nervous activation by means of Fourier analysis of pupillary oscillations might be useful in monitoring substitution therapy.

[Heparin-induced thrombocytopenia and hemofiltration: regional anticoagulation with sodium citrate]. / Heparin-induzierte Thrombozytopenie und Hämofiltration: Regionale Antikoagulation des extrakorporalen Kreislaufs mit Natriumcitrat.

The symptoms, diagnosis, and therapy for a septic patient with acute renal failure on continuous hemofiltration and heparin-anticoagulation who developed heparin-induced thrombocytopenia type II are described. Different alternatives for anticoagulation of extracorporal circulation are discussed. The principles of anticoagulation with sodium citrate are presented. It is necessary to closely monitor and, if need be, correct the serum calcium levels and acid base metabolism. We show that regional anticoagulation with sodium citrate is an effective and safe treatment.

Receptor test (pupillary dilatation after application of 0.01% tropicamide solution) and determination of central nervous activation (Fourier analysis of pupillary oscillations) in patients with Alzheimer's disease.

Memory loss and severe cognitive deficits in Alzheimer patients are supposed to be related to a reduction of acetylcholine as well as to central nervous deactivation. For the investigation of cholinergic deficits and deactivation, we used computer-assisted pupillometry. Cholinergic deficits caused by a particularly severe loss of cholinergic neurons may be responsible for cognitive and mnemonic performance deficits. The control of the pupillary diameter represents a balance between cholinergic and adrenergic innervation and is influenced directly or indirectly by central and autonomic nervous system inputs. Either of these systems could be affected in Alzheimer patients. A reduced innervation of the target muscle through neuronal cell death, axon retraction, reduced release, increased reuptake of altered amounts or function of neurotransmitter receptors seems to affect the pupillary response to cholinergic antagonists in Alzheimer patients. There is, however, no relationship between pupillary diameter and central deactivation, but between central nervous activation and pupillary oscillations which reflect the physiological corticodiencephalic activity, a relationship has to be assumed. Frequencies and amplitudes of pupillary oscillations measured by means of Fourier analysis are modulated corticodiencephalically. Therefore, Alzheimer patients were compared to healthy controls with respect to their pupillary diameters and responses to an acetylcholine antagonist. Twenty-nine patients, aged between 55 and 85 years, suffering from mild to moderate Alzheimer's disease (AD) and 29 normal controls of similar age (56-85 years) participated in the study. The cholinergic receptors of the pupil were blocked by the acetylcholine antagonist tropicamide. It could be assumed that the larger the pupillary dilatation, the larger the extent of cognitive deficits. Alzheimer patients show abnormal acetylcholine neurotransmission. Changes of pupillary diameter after instillation of 1 drop of 0.01% tropicamide solution were measured and Fourier analysis of pupillary oscillations was performed. Times of measurement were: 0 (baseline), 20, 40, 60, 80, and 100 min. After 4 min tropicamide was instilled. Forty min after the instillation of tropicamide into the left eye, the Alzheimer patients showed a pronounced dilatation of 41.57%. The dilatation in normal controls was 28.5%. Fourier analysis of pupillary oscillations (sum of frequency bands = power) demonstrated a marked deactivation (low amplitudes in low-frequency bands, but in contrast to our expectations no higher amplitudes in the higher frequency bands) in patients with AD which remained constant at all times of measurement. By means of discriminant analysis of pupillary diameter and pupillary oscillations (frequency band 0.00-1 Hz), 89. 7% were correctly predicted to be Alzheimer patients, 89% to be normal controls.

[Fourier analysis of pupil oscillations for measuring central activation in psychosomatic patients]. / Fourieranalyse der Pupillenoszillationen zur Messung der zentralen Aktiviertheit bei psychosomatischen Patienten.

The aim of the study was to answer the question if there are any differences in the central activation of different groups of psychosomatic patients and patients with eating disorders, which was measured by means of Fourier analysis of pupillary oscillations. A total of 132 patients (110 f, 22 m) with a mean age of 29.69 years (standard deviation: 9.9) participated in the study. In anorectic and bulimic patients high central activation was observed. Different groups of psychosomatic patients showed significant differences in their central nervous activation. In the group of subjects with the ICD-10 diagnosis F 41.3 (mixed anxiety disorders) the highest amplitudes was observed not only in the particular frequency bands but also in the total spectrum (power), which reflects high central activation. Reduced activation was found in subjects with somatoform autonomic function disorder of the upper and lower gastrointestinal tract (F 45.3). The measurement of central activation in psychosomatic disorders could have consequences for therapeutic interventions.

Psychophysiological diagnostics in alcohol dependency: Fourier analysis of pupillary oscillations and the receptor test for determination of cholinergic deficiency.

Mnestic disturbances in alcoholics may be related to cholinergic deficiency as well as to central nervous system inactivation. After instillation of tropicamide, cholinergic receptors are blocked and pupillary dilatation occurs. It is assumed that the more severe the cognitive deterioration, the wider the pupillary dilatation. Pupillary oscillations reflect central activation. Changes of pupillary diameter after topical instillation of tropicamide and pupillary oscillations were measured in 44 alcohol-dependent patients aged 40-55 years, diagnosed according to the DSM-III-R as severe alcoholics (>7 symptoms), having been abstinent for at least 3 weeks (objectively tested with carbohydrate-deficient transferrin), compared with 18 healthy controls. The pupillary diameter of the left eye was measured eight times within 103 min, as were pupillary oscillations. Using Fourier analysis, the amplitudes of oscillations were measured in five frequency bands and the sum of the frequency bands was calculated. In addition, central activation was measured during a calculation test at 3 and 103 min. The pupillary dilatation of 22% in alcoholics compared to 14% of normal controls after tropicamide raises the question of a cholinergic deficit in alcohol dependence. With regard to basic activation, measured by Fourier analysis of pupillary oscillations, alcoholics demonstrated significantly lower power (sum of the frequency bands) than controls at baseline and at 3, 20, and 40 min (P < 0.01) as well as at 60, 80, 100, and 103 min (P < 0.05). After a cognitive task, a difference between alcoholics and healthy controls was found at 3 min. Alcoholics showed lower basic activation and decreased cognitive activation. By means of cross-validation, a differentiation between alcohol-dependent patients (n = 44 and n = 42 respectively) and normal controls (n = 18) was possible.

[The "cognitive pupillary oscillation hypothesis" in patients with neurotic disorders and organic psychosyndrome: reliability and validity of a new psychophysiologic method]. / Die "Kognitive Pupillenoszillationshypothese" bei Patienten mit neurotischen Störungen bzw. organischem Psychosyndrom: Reliabilität und Validität eines neuen psychophysiologischen Verfahrens.

A new psychophysiological method called "cognitive pupillary oscillation hypothesis" is introduced. Under the influence of a cognitive test (simple calculations) changes of the maximal amplitudes of pupillary oscillations, reflecting central nervous activation, are observed. In healthy subjects a retest reliability of 0.75-0.85 was calculated. Furthermore, the data after FFT (Fast Fourier Transform) of pupillary oscillations of two populations of patients (n = 509 and 396, respectively) showed a high stability. The validity of the method was determined by means of a procedure similar to cross validation. The use of the "cognitive pupillary oscillation hypothesis" for the differential diagnosis between patients with neurotic disorders (ICD 9: 300) (n = 73) and patients with organic brain syndrome (ICD 9: 290, ICD 291.2) (n = 34) is demonstrated.

[A new method for testing the psychopharmacologic pupil oscillation hypothesis following administration of a nootropic substance]. / Eine neue Methode zur Uberprüfung der psychopharmakologischen Pupillenoszillations-Hypothese nach Verabreichung einer nootropen Substanz.

Recently a new, precise and economical method for measuring central nervous activation in psychopathological groups was presented. By means of this procedure, the ¿psychopharmacological pupillary oscillations hypothesis¿ after administration of the nootropic compound bifemelane (CAS 90293-01-9) was examined in oder to assess pharmacologically induced changes in central activation. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique, which is called ¿smoothing¿. After application of bifemelane, a marked improvement of symptoms caused by cerebro-vascular disorders was reported. 18 subjects (7 females and 11 males), aged between 60 and 80 years, with a neurological and psychic age-adequate state, from whom a written, informed consent was obtained, participated voluntarily in the study. A placebo-controlled and double-blind design were administered in an interval of 8 days in cross-over design. The study, which also included measurement of noopsychic and thymopsychic changes, was carried out before and in the 2nd, 4th, 6th and 8th hour after application of the substances. In the slow frequency band, after application of bifemelane, an increase of activation (higher amplitudes) could be observed, which lasted from the 2nd to the 4th hour. However, differences between bifemelane and placebo did not reach the level of statistical significance. In faster frequencies, a reduction of the height of the amplitudes was found. Regarding the total spectrum, in the 2nd hour a moderate increase of activation could be demonstrated.

[A new method for measuring central activation: fourier analysis of pupillary oscillations in depressed patients]. / Eine neue Methode zur Messung der zentralen Aktivierung: Fourieranalyse der Pupillenoszillationen bei depressiven Patienten.

While the changes in pupillary size during wakefulness and drowsiness are easy to understand, the origin of pupillary oscillations is quite mysterious. Waves of spontaneous pupillary constriction and dilation accompany periods of increasing sleepiness and spontaneous arousal. Lowenstein et al. (1963) demonstrated that in the dark, the pupils of young normal alert subjects show waves of dilatation and contraction lasting from about 4 to 40 s and measuring up to 0.5 mm. Furthermore, superimposed fast and very extensive oscillations were observed. The first described oscillations seemed to reflect central nervous activation. Therefore we analysed pupillary oscillations during the recording period of static pupillometry (described by the authors in 1992) which lasted for 25.6 s. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique which is called "smoothing". Using the Fourier analysis, the spectrum was divided into 5 frequency bands (0.0-0.2; 0.21-0.4; 0.41-0.60; 0.61-0.8; 0.81-1 Hz). We were also interested in the total spectrum. In order to demonstrate utilisation of the new technique, 146 male and female depressed patients (ICD-Diagnosis 296.1, 296.3, 296.1, 296.3 + 300, respectively, 300.4, 301.1, 296.1, 296.3 + 290, respectively), aged between 18 and 45 years, were investigated by means of pupillometry, followed by analysis of pupillary oscillations. The whole group of depressive patients who received antidepressive medication was compared with 64 healthy subjects of similar age to demonstrate differences in the frequency bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Pupillometry in clinical psychophysiological diagnostics: methodology and proposals for application in psychiatry.

The change in pupillary reactions may be considered as an important parameter of the autonomic nervous system. By means of pupillometry, it became possible to measure both objectively and economically these reactions. The method of microprocessor-assisted "static" and light evoked "dynamic" pupillometry is demonstrated. A high reliability for the static variable of pupillometry was also evaluated. Variables measured during "static and dynamic" pupillometry were factor-analyzed. Four factors (static, dynamic, stimulus specific and restitution dependent) were obtained regardless of whether investigations were carried out in normals or in psychiatric patients. Examples of utilization of pupillometry in psychopharmacology and mental disorders are also described in this essay.