Influence of acute psychological trauma on time estimation behaviour: a prospective pilot study.

In addition to the symptom triad of intrusions, avoidance behaviour and hyperarousal, typical and frequent characteristics of acute and chronic posttraumatic disorders are neuropsychological disturbances of working memory and executive functions. So far, however, only a very limited number of studies have dealt with their effects on the capability to assess time-related information. The purpose of this prospective study therefore was to compare persons after an acute traumatic experience with healthy controls in the course of 12 months, focusing on their ability to estimate time as a measure of their readiness of attention. 39 participants aged 17-59 years (mean age = 35.1 years, who had experienced a traumatic event and exhibited symptoms of acute stress disorder) were compared with 38 healthy controls (mean age = 36.1 years) at eight times of measurement within a period of 12 months. Performance was determined by means of a prospective time estimation task. The participants had to estimate a time interval of 5 s, once with and once without feedback about the quality of the estimates. The time estimates by the traumatised persons were significantly less precise than those by the control group. Progress analyses have shown that trauma patients exhibit larger deviations from the defined time interval, both under feedback conditions and without feedback. Psychological traumatisation leads to both an acute and long-term, demonstrable impairment of time estimation ability. The recognizable disturbance of information processing may both be a cause and a result of clinical trauma symptoms.

Aerobic exercise as a therapy option for migraine: a pilot study.

Exercise is assumed to have a positive effect on migraine. However, none of the few studies on this topic can prove the expected positive influence of exercise. Therefore, the aim of this pilot study was to develop a training program suitable for migraine patients and to examine its effect on migraine. 16 patients were examined. 8 migraine patients completed a 10-week aerobic running exercise program consisting of 3 workouts per week. The program was developed by sports scientists especially to increase the fitness level. Physical fitness, i. e., physical working capacity, was assessed using a PWC 150 test. There was also a control group of 8 patients without any special physical training. Migraine patients of the exercise group showed both a reduction in the number of migraine days per month (p=0.048) and the intensity of the attacks (p=0.028). An increase in fitness level resulted in a lowered stress level. Stress strategies like "displacement activity" (r=-0.715; p=0.046), "looking for self-affirmation" (r=-0.742; p=0.035) and "feelings of aggression" (r=-0.802; p=0.017) were reduced. Increasing the level of fitness (PWC 150) is one predictor for migraine improvement (r=0.409, p=0.031). Aerobic exercise which leads to a better fitness level is an alternative therapy method for migraine.

Effects of pregnancy on slow cortical potentials in migraine patients and healthy controls.

Increased negative amplitudes and lack of habituation of contingent negative variation (CNV) in migraine are well established and are supposed to reflect an altered cortical excitability level. Migraine attacks occur less during pregnancy but often relapse after delivery. We investigated the effect of pregnancy on slow cortical potentials and reaction time in migraine patients and healthy controls. Four groups were examined: 14 pregnant migraine patients, 12 non-pregnant migraine patients, 15 pregnant healthy women and 16 non-pregnant healthy women aged 19-38 years. Two recordings were performed in the pregnant subjects: in the 36th week of gestation and 4 weeks after delivery. The non-pregnant subjects were recorded at the same time interval of 8 weeks. Pregnant migraine patients showed significantly fewer migraine days during the third trimester of pregnancy and returned to nearly the former level 4 weeks post delivery. Non-pregnant migraine patients demonstrated a significant reduction of migraine days at the second measurement. There was no effect of pregnancy on CNV amplitudes, but there was an effect of pregnancy on the habituation coefficient and reaction time of migraine patients. Faster habituation from a higher preactivation level was found. As an explanation for the changed habituation level we favour the model of correlation between preactivation level and habituation level, the so-called law of initial value. We found a correlation between preactivation level and habituation. Our study confirms a specific effect of pregnancy on slow cortical potentials in migraine patients.

Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder.

INTRODUCTION: Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylphenidate preparation (Medikinet retard, MPH-MR), with equal portions of the immediate-release and the sustained-release active substance, and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology. METHODS: Eighty five children and adolescents (6-16 years) were investigated in a double-blind, randomized, clinical trial over 5 weeks under a treatment with MPH-MR using symptom checklists for ADHD, oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). RESULTS: A total of 64.9% of the children showed oppositional defiant disorder/conduct disorder (ODD/CD) symptoms. A statistically significant effect was found in the group treated with MPH (verum-group). On the basis of Cohen's criteria, high effects were found for aggressive symptoms in school (d = 1.0), but not in the afternoon (d = 0.4). There were also lower effect sizes for more severe aggressive symptoms. We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention. CONCLUSIONS: Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior, especially concerning milder symptoms. The expected correlation between impulsivity and aggressiveness could be confirmed.

Ten novel BRCA1 and BRCA2 mutations in breast and/or ovarian cancer families from northern Germany.

Germline mutations in the BRCA1 and BRCA2 gene account for the majority of high-risk breast/ovarian cancer families. We have screened such families from Northern Germany by using DHPLC analysis and subsequent direct sequencing techniques. In ten families we identified six novel BRCA1 and 4 novel BRCA2 mutations comprising four frame shift mutations, one nonsense and one splice site mutation in the BRCA1 gene as well as three frameshift mutations and one nonsense mutation in the BRCA2 gene. Our analysis contributes to the further characterisation of the mutational spectrum of BRCA1 and BRCA2.

Analgesic-induced chronic headache: long-term results of withdrawal therapy.

Headache characteristics are described in 139 patients with chronic daily or almost daily headaches due to regular intake of analgesics and the short- and long-term results of drug withdrawal. Drug-induced headache was described as dull, diffuse, and band-like, and usually started in the early morning. The mean duration of the original headache (migraine or tension headache) was 25 years; regular intake of drugs and chronic daily headache had started 10 and 6 years prior to withdrawal therapy, respectively. Patients took an average of 34.6 tablets or analgesic suppositories or antimigraine drugs per week containing 5.8 different substances. The drugs most often used were caffeine (95%), ergotalkaloids (89%), barbiturates (64%), and spasmolytics, paracetamol, and pyrazolone derivates (45%-46%). A total of 103 patients (68 migraine, 35 tension or combination headache) were available for interviews at a mean time interval of 2.9 years after an inpatient drug withdrawal programme. Chronic headache had disappeared or was reduced by more than 50% in two-thirds of the patients. Positive predictors for successful treatment were migraine as primary headache, chronic headache lasting less than 10 years, and regular intake of ergotamine. Drug intake was significantly reduced and patients used single substances more often. Patients who originally suffered from migraine, superimposed on the daily headache, also experienced a significant improvement in the frequency of the migraines and their intensity. Migraine prophylaxis through beta-blocking agents and calcium channel antagonists was more efficient after drug-withdrawal therapy.

Prediction of migraine attacks using a slow cortical potential, the contingent negative variation.

Amplitudes of contingent negative variation (CNV) as a slow cortical potential in migraine patients were recorded before and after migraine attacks. The level of CNV amplitudes, especially of the early component, showed a trend in rise of negativity 1 day before the attack, whereas amplitudes were normal for 2-3 days following an attack. In most cases the attack occurred when the CNV amplitude showed maximum negativity. We conclude that migraine-susceptible days are indicated by a high CNV amplitude the day before the attack.

Migraine in childhood--are periodically occurring migraine attacks related to dynamic changes of cortical information processing?

Amplitudes and habituation of contingent negative variation (CNV) were analyzed in relation to spontaneously occurring migraine attacks in ten children suffering from migraine without aura. Recording took place during feedback training and instrumental conditioning of slow brain potentials. Both the amplitude of the early CNV component and its habituation deficit increase during the 5 days prior to a migraine attack, with maximum abnormalities the day before the ictal episode. Abrupt reduction of the amplitude and normalization of the CNV habituation were observed during the attack. This study provides evidence for neurophysiological periodicity in young migraineurs and emphasizes that the time relative to the migraine attacks must be considered in studies of juvenile migraine during the headache-free period.

Migraine--evidence for a disturbance of cerebral maturation in man?

The contingent negative variation (CNV), a slow cortical potential between two defined stimuli, was used to record the effect of age in 162 migraine patients and 320 healthy controls aged between 8 and 59 years. The early component (iCNV) and habituation slope of 32 GO-trials are presented. There were no significant differences between healthy controls and migraine patients in iCNV amplitudes or habituation slope up to the age of 19 years. In the age groups from 20-59 years the healthy controls showed a significantly reduced iCNV compared with migraine patients and healthy controls below 20 years of age. While the habituation slope increased in healthy controls, there was no habituation of iCNV in migraine patients. It is suggested that reduced iCNV amplitudes in healthy controls indicate a state of cerebral maturation. This maturation effect is missing in adult migraine patients, leading to pronounced attentional effort in these patients.

Contingent negative variation indicates phasic arousal for externally cued unilateral eye blink in human subjects.

The contingent negative variation (CNV) as a slow cortical potential was used to investigate cortical processing of externally cued, voluntary unilateral eye blink. Probands blinked as a response within a modified two-stimulus reaction time paradigm. Reaction time and amplitudes of CNV were determined. The activity of the orbicularis oculi muscles (OO) was registered by surface electromyography (EMG). Probands who performed unilateral eye blinks with accurately inhibiting contralateral OO activity showed a significantly higher negativity of the early CNV component compared with the bilateral eye blink condition. This effect was confined to the beginning of unilateral blinking performance. It is suggested that the unilateral eye blink is a challenging motor task, initially requiring an increased cortically driven arousal and attention as revealed by increased early CNV components.

Non-linear electroencephalogram dynamics in patients with spontaneous nocturnal migraine attacks.

The present study was conducted to examine non-linear electroencephalogram (EEG) measures during the development of a spontaneous migraine attack. We investigated the sleep EEG of five patients with migraine without aura in the pain-free interval and at the onset of a nocturnal attack. Sleep EEG recordings were analysed using the method of global dimensional complexity compared to conventional sleep scoring techniques. We found no divergence between classical sleep architecture and the estimated dimensional course nor any relevant short-term changes related to the onset of headache. There was, however, a loss of dimensional complexity in the first two non-rapid eye movement sleep states in the migraine night, with statistical significance during the second sleep cycle. For the first time, these results provide evidence of a global dimension decrease that is related to cortical network changes during a migraine attack.

Contingent negative variation and attentional performance in humans.

The relation between a paper-pencil test of sustained attention (d2-letter cancellation test, d2-LCT) and the contingent negative variation (CNV) as a cortical slow potential was calculated in 23 healthy undergraduate students. Both d2-LCT and CNV reflect selective, focussed attention. There was a Pearson correlation coefficient of r = -0.670 between the early component of the CNV and the number of checked letters in d2-LCT, indicating significant differences in early CNV between low and high performance in d2-LCT. The results showed a linear relationship between paper-pencil registered attentional properties and the cortically recorded early component of CNV.

Contingent negative variation as indicator of duration of migraine disease.

Amplitudes of early wave contingent negative variation (iCNV) reveal significant differences between migraine patients and healthy controls, indicating a lack of habituation and pronounced attentional functions in migraine patients. CNV amplitudes were recorded in 20 migraine patients. The CNV amplitudes were Pearson correlated with the individual duration of the migraine disease. Only iCNV correlates inversely with the duration (r = -.544). The data show an influence of duration of migraine disease on iCNV amplitudes. It is suggested that iCNV is an indicator of chronicity in persistent migraine.

Clinical efficacy and central mechanisms of cyclandelate in migraine: a double-blind placebo-controlled study.

The mechanisms of action of calcium antagonists in the prophylactic treatment of migraine remain unclear. The most likely proposed mechanism seems to be via influence on the central nervous system, but the central effects of calcium entry blockers are insufficiently characterized. The aim of the present study was to investigate the central mechanisms behind the efficacy of cyclandelate in a double-blind placebo-controlled parallel-designed study using the contingent negative variation (CNV), an event-related slow potential for measuring cortical excitability and investigating preparation processes. The CNV recordings were performed in 25 females suffering from migraine without aura before treatment (baseline), after single dose administration of cyclandelate or placebo and after 8 weeks' treatment with cyclandelate (cyclandelate group, no.=15) or placebo (placebo group, no.=10). Cyclandelate reduced significantly the days with migraine and duration of migraine compared to placebo. In the cyclandelate group a significant reduction of all CNV components was observed and the changes in amplitudes compared to baseline were more pronounced after treatment. Placebo reduced the late CNV component only after single dose administration. There were no changes in the early and total CNV. Cyclandelate did not normalize the habituation of the slow negative potential. The results are discussed in terms of the influence of cyclandelate on cortical excitability and of the prevention of cortical spreading depression via antagonistic effect on calcium channels.

How the brain anticipates an attack: a study of neurophysiological periodicity in migraine.

We investigated cortical excitability and the pattern of arousal in migraine patients using contingent negative variation (CNV) and EEG power spectrum analysis performed before and after a migraine attack. Twenty females suffering from migraine without aura and 12 healthy controls were enrolled in the study. In the group of patients, the CNV, EEG power spectrum and hemispheric asymmetry analyses were performed 1-4 days before the first day of an attack and 4 days following the last day with migraine. The recordings in healthy subjects were carried out on a day chosen by the participants. The comparisons were made using non-parametric procedures. After an attack no difference was found between patients and controls in EEG power spectrum, hemispheric asymmetry or CNV components (with the exception of the beta 1 power, which was more pronounced in patients). Before an attack, however, a significant increase in the power of delta and theta frequency bands, in the alpha asymmetry, and in early CNV amplitude were observed. The patients differed from controls both in the extent of cortical excitability and in the arousal pattern found. In such a way migraine is characterized by periodic CNV and EEG power spectrum changes during the pain-free interval. The abnormalities in cortical excitability and arousal were only observed before an attack, and could be used to predict the next migraine episode. We assume that these changes reflect the increased susceptibility of the migrainous brain to precipitating factors and the neurophysiological readiness to generate an attack. The time duration since the last attack must be taken into account when performing studies in the field of migraine research.

Behavioral treatment in migraine. Cognitive-behavioral therapy and blood-volume-pulse biofeedback: a cross-over study with a two-year follow-up.

The aim of the present study was to ascertain the effects of two behavioral medicine approaches to the treatment of migraine. We also evaluated the specific effect of the sequence of the two treatments. Thirty-eight patients, suffering from migraine without aura, either obtained treatment in the following sequence: blood-volume-pulse biofeedback followed by cognitive behavioral therapy (Group I) or were given the treatment in reverse order (Group II). The effects of treatment in Group I were significantly better than those in Group II. We conclude that the application of biofeedback helps the patient to recognize the influence of thoughts and emotions on bodily reactions and therefore prepares the way for successful cognitive treatment.

Cyclandelate versus propranolol in the prophylaxis of migraine--a double-blind placebo-controlled study.

The aim of the present study was to ascertain the comparative efficacy of cyclandelate, a migraine prophylactic with calcium overload blocking properties, versus propranolol, a non-selective beta-adrenergic blocker, and placebo. Based on different statistical analysis procedures (including time series analysis) a responder and nonresponder evaluation for cyclandelate and propranolol was performed. In addition, an attempt was made to identify the dose relationship of the various drugs on headache parameters. In a double-blind placebo-controlled study 84 patients were treated in a placebo run-in phase (4 weeks). The patients were then randomized by the statistical criterion of placebo responder and nonresponder to either the cyclandelate or the propranolol group. The total treatment period included a low-dosage phase (8 weeks) and high-dosage phase (8 weeks). All patients kept a headache diary before, during and after treatment. The data were assessed by time series analysis (ARIMA), as well as by analysis of variance and nonparametric statistics. Based on ARIMA statistics, 39.3% of the patients showed a significant improvement of migraine during treatment with cyclandelate compared with 29.4% placed on propranolol. Higher doses of cyclandelate and propranolol were more effective. Using the qualitative response-criterion of a 50% reduction in migraine symptoms, cyclandelate showed a response in 67.9% and propranolol in 41.2% of all cases. It can therefore be concluded that cyclandelate as well as propranolol are two comparable substances in the prophylactic treatment of migraine, with cyclandelate showing fewer side effects.

[Compliance problems and behavioral medicine implications in the drug therapy of pain]. / Complianceprobleme und verhaltensmedizinische Implikationen bei der medikamentösen Schmerztherapie.

Many patients, even cancer patients do not take their medication at all or at the prescribed dose showing thus a form of noncompliance. Reasons for this are manyfold and differ from patient to patient. They may undergo dynamic changes in the course of disease. Experience shows, that compliance is mainly improved when patients have the impression to be responsible for their comportment. This is an important goal in therapy of patients with chronic pain. Of particular importance is therefore the doctor-patient relation, i.e. non-compliance thus always indicates a disturbed doctor-patient relation.