Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine.

OBJECTIVE: Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation. METHODS: Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform. RESULTS: Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz. CONCLUSIONS: An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment. SIGNIFICANCE: These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization.

Multiscale analysis of short term heart beat interval, arterial blood pressure, and instantaneous lung volume time series.

MOTIVATIONS: Physiological systems are ruled by mechanisms operating across multiple temporal scales. A recently proposed approach, multiscale entropy analysis, measures the complexity at different time scales and has been successfully applied to long term electrocardiographic recordings. The purpose of this work is to show the applicability of this methodology, rooted on statistical physics ideas, to short term time series of simultaneously acquired samples of heart rate, blood pressure and lung volume, from healthy subjects and from subjects with chronic heart failure. In the same spirit, we also propose a multiscale approach, to evaluate interactions between time series, by performing a multivariate autoregressive (AR) modeling of the coarse grained time series. METHODS: We apply the multiscale entropy analysis to our data set of short term recordings. Concerning the multiscale version of the multivariate AR approach, we apply it to the four dimensional time series so as to detect scale dependent patterns of interactions between the physiological quantities. RESULTS: Evaluating the complexity of signals at the multiple time scales inherent in physiologic dynamics, we find new quantitative indicators which are statistically correlated with the pathology. Our results show that multiscale entropy calculated on all the measured quantities significantly differs (P<10(-2) and less) in patients and control subjects, and confirms the complexity-loss theory of aging and disease. Also applying the multiscale autoregressive approach significant differences were found between controls and patients; in the sight of finding a possible diagnostic tools, satisfactory results came also from a receiver-operating-characteristic curve analysis (with some values above 0.8). CONCLUSIONS: The multiscale entropy analysis can give useful information also when only short term physiological recordings are at disposal, thus enlarging the applicability of the methodology. Also the proposed multiscale version of the multivariate regressive analysis, applied to short term time series, can shed light on patterns of interactions between cardiorespiratory variables.

Red blood cell (RBC) surface acetylcholinesterase showing a hemorheological pattern during glaucoma treatment.

BACKGROUND: Glaucoma is currently attributed to two different possible pathogenetic mechanisms: mechanical (the ocular damage is induced by physical injury), and vascular (the ocular damage is sustained by ischemia of the optic nerve head). AIM: We considered the possibility that several anti-glaucoma drugs (beta-blockers, carbonic anhydrase inhibitors and prostaglandins) could have an influence on optic nerve head hemorheology and oxygen supply. MATERIALS AND METHOD: We studied 4 groups of 10 subjects each: a control group, and 3 primary open angle glaucoma (POAG) groups, treated with topical beta-blockers, (10 patients), carbonic anhydrase inhibitors (CAI), and prostaglandin analogs (PG), respectively. In these 4 groups we investigated the RBC surface AchE and cytosolic calcium levels in order to assess their possible influence on the hemorheology and microcirculation in optic nerve head blood perfusion. RESULTS: A significant correlation (p < 0.048) was found between the RBC surface acetylcholinesterase and RBC intracytosolic calcium values in patients with POAG treated with beta-blockers. We found no significant correlation (p = n.s.) between the same patterns in the other Groups or in Controls. CONCLUSION: These data indicate that CAI and PG drugs do not interfere with AchE in POAG patients, whereas beta-blockers negatively affect the RBC deformability.

Visually evoked phase synchronization changes of alpha rhythm in migraine: correlations with clinical features.

OBJECTIVE: This study aimed to compute phase synchronization of the alpha band from a multichannel electroencephalogram (EEG) recorded under repetitive flash stimulation from migraine patients without aura. This allowed examination of ongoing EEG activity during visual stimulation in the pain-free phase of migraine. METHODS: Flash stimuli at frequencies of 3, 6, 9, 12, 15, 18, 21, 24, and 27 Hz were delivered to 15 migraine patients without aura and 15 controls, with the EEG recorded from 18 scalp electrodes, referred to the linked earlobes. The EEG signals were filtered in the alpha (7.5-13 Hz) band. For all stimulus frequencies that we evaluated, the phase synchronization index was based on the Hilbert transformation. RESULTS: Phase synchronization separated the patients and controls for the 9, 24 and 27 Hz stimulus frequencies; hyper phase synchronization was observed in patients, whereas healthy subjects were characterized by a reduced phase synchronization. These differences were found in all regions of the scalp. CONCLUSIONS: During migraine, the brain synchronizes to the idling rhythm of the visual areas under certain photic stimulations; in normal subjects however, brain regions involved in the processing of sensory information demonstrate desynchronized activity. Hypersynchronization of the alpha rhythm may suggest a state of cortical hypoexcitability during the interictal phase of migraine. SIGNIFICANCE: The employment of non-linear EEG analysis may identify subtle functional changes in the migraine brain.