Anna Montemurno

Laser-evoked potential habituation and central sensitization symptoms in childhood migraine.

Objectives Few studies have addressed central sensitization symptoms and pain processing in childhood migraine. Our aims were to examine pain sensitivity and responses, including habituation, evoked by CO2 laser stimuli (laser-evoked potentials (LEPs)) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization. Methods Thirty-five patients 8–15 years of age with migraines without aura were evaluated during the inter-critical phase and were compared to 17 controls. LEPs were analyzed, and their main features were correlated with clinical symptoms including allodynia and pericranial tenderness. Results The laser-evoked pain threshold was lower and the N2P2 vertex complex amplitude was higher in children with migraines. Furthermore, habituation of vertex waves of LEPs clearly showed a tendency toward progressive amplitude enhancement in the migraine group. Acute allodynia and inter-critical pericranial tenderness correlated with trigeminal LEP features, particularly with the abnormal habituation pattern. Discussion Abnormalities of pain processing and symptoms of central sensitization appear to be characteristics of children with migraine. Reduced habituation and progressive amplification of cortical responses to laser stimuli indicate an overactive nociceptive system at the onset of migraine, and this hyperactivity may subtend allodynia and pericranial tenderness. Future prospective trials may aid in the early identification of clinical phenotypes that display a tendency to develop into the chronic form of migraine, warranting a timely therapeutic approach.

Age‐related changes in laser‐evoked potentials following trigeminal and hand stimulation in healthy subjects

This study aimed to evaluate age‐related changes in laser‐evoked potential (LEP) features, including habituation, via trigeminal and hand stimulation in a large group of healthy volunteers.

Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission.

Effects of left primary motor and dorsolateral prefrontal cortex transcranial direct current stimulation on laser-evoked potentials in migraine patients and normal subjects.

Migraine is characterized by an altered cortical excitability. Because transcranial direct current stimulation (tDCS) can change brain activity noninvasively, it is possible to hypothesize its efficacy in modulating pain in migraine. In this study, we compared the effects of tDCS of the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) both on subjective pain and on evoked responses induced by laser stimulation (LEPs). Thirty-two patients and sixteen controls were randomized to receive sham stimulation and real tDCS with the anode centered over M1 or DLPFC. Laser Evoked potentials were recorded in basal, sham and tDCS conditions. We did not find significant acute changes in LEPs parameters and pain perception among subjects who received tDCS of both M1 and DLPFC. After DLPFC tDCS, we observed a significant increase of N2-P2 component habituation in migraine patients while M1 stimulation reduced it. These findings may suggest a modulation of abnormal pain processing induced by DLPFC and M1 anodal tDCS and outline the need for future investigations exploring the possible neuronal plasticity changes supporting the clinical effect on migraine.

Laser Evoked Potentials in Early and Presymptomatic Huntington's Disease.

Pain was rarely studied in Huntingtons disease (HD). We presently aimed to extend our previous study on pain pathways functions by laser evoked potentials (LEPs) to a larger cohort of early unmedicated HD patients and a small group of presymptomatic HD (PHD) subjects. Forty-two early HD patients, 10 PHD patients, and 64 controls were submitted to LEPs by right-hand stimulation. Two series of 30 laser stimuli were delivered, and artifact-free responses were averaged. The N1, N2, and P2 latencies were significantly increased and the N2P2 amplitude significantly reduced in HD patients compared to controls. In the HD group, the LEPs abnormalities correlated with functional decline. PHD subjects showed a slight and insignificant increase in LEPs latencies, which was inversely correlated with the possible age of HD clinical onset. Data of the present study seem to suggest that the functional state of nociceptive pathways as assessed by LEPs may be a potential biomarker of disease onset and progression. The assessment of pain symptoms in premanifest and manifest HD may also open a new scenario in terms of subtle disturbances of pain processing, which may have a role in the global burden of the disease.

Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine

In previous studies, migraine patients showed abnormalities in pain-related evoked responses, as reduced habituation to repetitive stimulation. In this study, we aimed to apply a novel analysis of EEG bands synchronization and directed dynamical influences under painful stimuli in migraine patients compared to non-migraine healthy volunteers. Thirty-one migraine without aura outpatients (MIGR) were evaluated and compared to 19 controls (CONT). The right hand was stimulated by means of 30 consecutive CO2 laser stimuli. EEG signal was examined by means of Morlet wavelet, synchronization entropy (SE), and Granger causality (GC), and the statistically validated results were mapped on the corresponding scalp locations. The vertex complex of averaged laser-evoked responses (LEPs) showed reduced habituation compared to CONT. In the prestimulus phase, enhanced SE in the 0, 5–30 Hz range was present in MIGR and CONT between the bilateral temporal–parietal and the frontal regions around the midline. Migraine patients showed an anticipation of EEG changes preceding the painful stimulation compared to CONT. In the poststimulus phase, the same cortical areas were more connected in MIGR vs CONT. In both groups of patients and CONT, the habituation index was negatively correlated with the GC scores. A different pattern of cortical activation after painful stimulation was present in migraine. The increase in cortical connections during repetitive painful stimulation may subtend the phenomenon of LEPs reduced habituation. Brain network analysis may give an aid in understanding subtle changes of pain processing under laser stimuli in migraine patients.

A P300 Clustering of Mild Cognitive Impairment Patients Stimulated in an Immersive Virtual Reality Scenario

In this paper, we present an innovative framework useful for clustering patients affected by a mild cognitive impairment and designed to improve the living environment and the lifestyle of patients in order to delay their cognitive state decline. The cognitive state changes are evaluated by means the event - related potentials elicited by environmental stimuli administered in several Virtual Reality scenarios. In particular, we formerly describe our innovative Virtual Reality environment, the protocol of stimuli administration, the procedure to measure the P300 latency in the response signal and finally the Self Organizing Map used to cluster the data. This research finds application in the fields of re-qualification of the environments for patients and healthcare introducing a new method for evaluation of best living conditions through VR.

P042. Mechanism of action and clinical evidence of botulinum toxin in chronic migraine

Considerable evidence exists supporting the notion that botulinum toxin type A (BoNT/A) can exert a direct analgesic effect in addition to its myorelaxant effect. It is likely that the benefict of using BoNT/A as prophylactic treatment for chronic migraine is due to its ability to inhibit overactivity of motor neurons and hyperexcitability of sensory neurons, by involving the suppression of peripheral and central sensitization. In this study we aimed to evaluate the effects of BoNT/A on amplitude, latency and habituation of laser evoked potentials (LEPs) in patients with chronic migraine. We recruited 20 patients with a diagnosis of chronic migraine treated with type A botulinum toxin every 3 months. LEPs were recorded in basal, two hours and ten days after both BoNT/A and placebo injection. Headache frequency, allodynia and total tenderness score (TTS) were evaluated at basal condition and after one-year of treatment. We found N2 and P2 latency increased 10 days after toxin injection, while LEPs amplitude was not modified. Compared to placebo injection, the habituation of N2/P2 LEPs component obtained by stimulating supraorbital zone was significantly increased after BoNT/A infiltration. After ten days, habituation pattern in migraine patients was similar to that of normal subjects. In the one-year follow-up we observed a significant migraine frequency and allodynia improvement, but no effect on total tenderness score. Furthermore the habituation change correlated with the clinical effectiveness. Study results suggest a toxin modulating action on nociceptive afferents in patients with chronic migraine. The N2 and P2 latency increase obtained from hand laser stimulation suggests a possible systemic pain inhibiting effect. Although the botulinum toxin did not show an inhibitory effect on trigeminal nociceptive system, it seems to improve the reduced habituation pattern which promotes the central sensitization. The therapeutic effect of BoTN/A seemed to be related to the effect on trigeminal habituation obtained after 10 days from the first infiltration, which could be considered as a potential neurophysiological pattern to predict the non-responders. Results of this study confirm that the effect of botulinum toxin on chronic migraine may be related to a modulation and normalization of central sensitization mechanisms. The lack of effects on pericranial muscle tension precludes to suppose a modulating effect on trigeminal nociception by the inhibition of the neuromuscular synapse. Written informed consent to publish was obtained from the patient(s).

Bioelectrical Correlates of Emotional Changes Induced by Environmental Sound and Colour: From Virtual Reality to Real Life

Patients with age-related mild cognitive impairments could be better assisted in hospitals and nursing homes where innovative systems provide personalized cognitive rehabilitation or physical and recreational activities.

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

Background A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM). We aimed to correlate laser evoked potentials (LEPs), Sympathetic Skin Response (SSR), and clinical features in FM patients. Methods Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ) and severity scores (WPI), anxiety (SAS) and depression (SDS) scales, and questionnaires for neuropathic pain (DN4). Results The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32%) with higher DN4 and FIQ scores, SSR or LEP responses were absent. Conclusions LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients.