Search

Background/Objectives: Chronic migraine with medication-overuse headache (CM-MOH) is neurophysiologically characterized by increased cortical excitability with sensitization at both the thalamocortical and the cortical levels. It is unclear whether the increased cortical excitability could be reverted by medication withdrawal (i.e., brain state) or whether it is a brain trait of individuals predisposed to medication overuse. In this study, we aim to investigate whether withdrawal from overused drugs can influence and restore these neurophysiological abnormalities. Methods: Somatosensory evoked potentials (SSEPs) were elicited by electrical stimulation of the median nerve (M), the ulnar nerve (U), and the simultaneous stimulation of both nerves (MU) in 14 patients with CM-MOH before (T0) and after (T1) a three-week withdrawal protocol and, for comparison, in 14 healthy volunteers (HVs) of a comparable age distribution. We measured the level of thalamocortical (pre-HFO) and cortical activation (post-HFO) by analyzing the high-frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Furthermore, we calculated the habituation and the degree of cortical lateral inhibition (dLI) of N20-P25 low-frequency SSEPs. Results: After the three-week withdrawal protocol (T1), we observed a normalization of the baseline habituation deficit (T0: +0.10 ± 0.54; T1: −0.53 ± 0.8; p = 0.040) and a reduction in the amplitude for both pre-HFO (p < 0.009) and post-HFO (p = 0.042), with values comparable to those of the HVs. However, no effects were observed on the dLI (p = 0.141). Conclusions: Our findings showed that withdrawal from overused drugs could affect the increased excitability of the non-painful somatosensory system in patients with CM-MOH, reducing the level of sensitization at both the thalamocortical and the cortical levels. [ABSTRACT FROM AUTHOR]

Background/Hypothesis: Motion sensitivity symptoms, such as dizziness or unsteadiness, are frequently reported as non-headache symptoms of migraine. Postural imbalance has been observed in subjects with vestibular migraine, chronic migraine, and aura. We aimed to assess the ability of largest Lyapunov's exponent for a short time series (sLLE), which reflects the ability to cope with internal perturbations during gait, to detect differences in local dynamic stability between individuals with migraine without aura (MO) with an episodic pattern between attacks and healthy subjects (HS). Methods: Trunk accelerations of 47 MO and 38 HS were recorded during gait using an inertial measurement unit. The discriminative ability of sLLE was assessed through receiver-operating characteristics curves and cutoff analysis. Partial correlation analysis was conducted between the clinical and gait variables, excluding the effects of gait speed. Results: MO showed higher sLLE values, and reduced pelvic rotation, pelvic tilt, and stride length values. sLLEML and pelvic rotation showed good ability to discriminate between MO and HS and were correlated with the perceived pain, migraine disability assessment score, and each other. Conclusions: these findings may provide new insights into the postural balance control mechanism in subjects with MO and introduce the sLLEML as a potential measure of dynamic instability in MO. [ABSTRACT FROM AUTHOR]

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analysing the amplitude of the first block (100 sweeps) and to evaluate habituation by measuring the amplitude response decrement after six blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEP parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication withdrawal. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli. [ABSTRACT FROM AUTHOR]

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24–48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients. [ABSTRACT FROM AUTHOR]

We investigated the potential correlation between morphological and functional parameters describing the rarefaction and dysfunction of retinal ganglion cells (RGCs), located in the macula, in multiple sclerosis eyes with a history of optic neuritis (MS-ON). A total of 19 MS-ON eyes from 19 MS patients (mean age: 44.16 ± 4.66 years; 11 females and 8 males), with a mean disease duration of 10.06 ± 6.12 years and full recovery of visual acuity, and 30 age-similar (mean age: 45.09 ± 5.08 years) healthy eyes were submitted for ophthalmological evaluation using swept-source optical coherence tomography (SS-OCT) and multifocal photopic negative response (mfPhNR) to study the structural and functional features of localized RGCs. Both GCL+ thickness (via SS-OCT) and response amplitude density (RAD) (via mfPhNR) measurements were obtained from annular regions and ETDRS sectors. Morphological and electrophysiological data from the control and MS groups were compared by using an ANOVA test. GCL+ values were correlated with the corresponding RADs derived from almost superimposable areas using Pearson's tests (p < 0.01). In MS-ON eyes, the mean values of macular GCL+-T and mfPhNR RAD detected in all rings and ETDRS sectors were significantly reduced (p < 0.01) when compared with control ones. In addition, when plotting the GCL+-T and mfPhNR RAD individual data from MS-ON eyes, we found statistically significant linear correlations (p < 0.01) when considering responses from both rings and sectors. In conclusion, in MS-ON eyes, a topographical correlation between structural and functional impairment of macular RGCs occurs. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the morpho-functional involvement of the retinal ganglion cells (RGCs) and of the visual pathways in patients with superficial (ODD-S) or deep (ODD-D) optic disc drusen. This study enrolled 17 patients with ODD (mean age of 59.10 ± 12.68 years) providing 19 eyes and 20 control subjects (mean age 58.62 ± 8.77 years) providing 20 eyes. We evaluated the following: best-corrected visual acuity, visual field mean deviation (MD), the amplitude (A) of Pattern Electroretinogram (PERG), the implicit time (IT) and A of Visual Evoked Potentials (VEPs), retinal nerve fiber layer thickness (RNFL-T) and ganglion cell thickness (GC-T). In ODD-S eyes, the drusen visible height was measured. ODD-D and ODD-S were detected in 26.3% and 73.7% of ODD eyes, respectively. Significantly (p < 0.01) reduced MD, PERG A, VEP amplitude, RNFL-T and GC-T values and significantly (p < 0.01) increased VEP IT values were found in the ODD Group as compared to the Control one. In the ODD Group, no significant correlation (p > 0.01) between PERG As and VEP ITs was found. In ODD-S, the visible height was significantly correlated (p < 0.01) with reduced MD, PERG As and RNFL-T and with increased PSD and VEP IT values. Our findings suggest that ODD might induce morpho-functional changes in RGCs and their fibers and an unrelated visual pathway dysfunction leading or not leading to visual field defects. The observed morpho-functional impairment should be ascribed to an alteration in retrograde (from the axons to the RGCs) and anterograde (from the RGCs up to the visual cortex) axoplasmic transport. In ODD-S eyes, a minimum visible height of 300 microns represented the threshold for the abnormalities, suggesting that "the higher the ODD, the worse the impairment". [ABSTRACT FROM AUTHOR]

(1) Background: OnabotulinumtoxinA (BoNT-A) is a commonly used prophylactic treatment for chronic migraine (CM). Although randomized placebo studies have shown its clinical efficacy, the mechanisms by which it exerts its therapeutic effect are still incompletely understood and debated. (2) Methods: We studied in 15 CM patients the cephalic and extracephalic nociceptive and lemniscal sensory systems using electrophysiological techniques before and 1 and 3 months after one session of pericranial BoNT-A injections according to the PREEMPT protocol. We recorded the nociceptive blink reflex (nBR), the trigemino-cervical reflex (nTCR), the pain-related cortical evoked potential (PREP), and the upper limb somatosensory evoked potential (SSEP). (3) Results: Three months after a single session of prophylactic therapy with BoNT-A in CM patients, we found (a) an increase in the homolateral and contralateral nBR AUC, (b) an enhancement of the contralateral nBR AUC habituation slope and the nTCR habituation slope, (c) a decrease in PREP N-P 1st and 2nd amplitude block, and (d) no effect on SSEPs. (4) Conclusions: Our study provides electrophysiological evidence for the ability of a single session of BoNT-A injections to exert a neuromodulatory effect at the level of trigeminal system through a reduction in input from meningeal and other trigeminovascular nociceptors. Moreover, by reducing activity in cortical pain processing areas, BoNT-A restores normal functioning of the descending pain modulation systems. [ABSTRACT FROM AUTHOR]

Friedreich's ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations are ocular motility abnormality, optic neuropathy, and retinopathy. Despite the evidence of ophthalmological impairment in FRDA patients, there is a lack of information about the morpho-functional condition of the retina and of the optic pathways in healthy heterozygous carriers of Friedreich's ataxia (C-FRDA). Ten C-FRDA subjects (providing 20 eyes) and thirty-five Controls (providing 70 eyes) underwent a complete neurological and ophthalmological examination comprehensive of functional (full-field Electroretinogram (ffERG), multifocal Electroretinogram (mfERG), Visual Evoked Potential (VEP), and Pattern Reversal Electroretinogram (PERG)) and morphological assessments (Optical Coherence Tomography, OCT) of the retina, macula, retinal ganglion cells, and visual pathways. The groups' data were compared using a two-sample t-test. Pearson's test was used to investigate the morpho-functional correlations. Statistically significant differences (p < 0.01) between C-FRDA and Control eyes for the values of the following parameters were found: ffERG b-wave amplitude, mfERG Response Amplitude Densities, PERG P50 implicit time and P50-N95 amplitude, VEP P100 implicit time, Retinal Nerve Fiber Layer (RNFL) Overall, and Nasal thickness. The values of the OCT macular volume were not statistically different (p > 0.01) between the two Groups. Therefore, our data suggest that, in C-FRDA, a dysfunction of retinal elements without morphological macular impairment may occur. In addition, a morphological impairment of RNFL associated with an abnormal neural conduction along the visual pathways can be also detected. [ABSTRACT FROM AUTHOR]

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack. [ABSTRACT FROM AUTHOR]

A neuronal dysfunction based on the imbalance between excitatory and inhibitory cortical-subcortical neurotransmission seems at the basis of migraine. Intercritical neuronal abnormal excitability can culminate in the bioelectrical phenomenon of Cortical Spreading Depression (CSD) with secondary involvement of the vascular system and release of inflammatory mediators, modulating in turn neuronal activity. Neuronal dysfunction encompasses the altered connectivity between the brain areas implicated in the genesis, maintenance and chronic evolution of migraine. Advanced neuroimaging techniques allow to identify changes in functional connectivity (FC) between brain areas involved in pain processes. Through a narrative review, we re-searched case-control studies on FC in migraine, between 2015 and 2020, by inserting the words migraine, fMRI, EEG, MEG, connectivity, pain in Pubmed. Studies on FC have shown that cortical processes, in the neurolimbic pain network, are likely to be prevalent for triggering attacks, in response to predisposing factors, and that these lead to a demodulation of the subcortical areas, at the basis of migraine maintenance. The link between brain dysfunction and peripheral interactions through the inhibition of CGRP, the main mediator of sterile migraine inflammation needs to be further investigated. Preliminary evidence could suggest that peripheral nerves inference at somatic and trigeminal levels, appears to change brain FC. [ABSTRACT FROM AUTHOR]