Visual migraine aura iconography: A multicentre, cross-sectional study of individuals with migraine with aura.

INTRODUCTION: Visual disturbances are the most common symptoms of migraine aura. These symptoms can be described systematically by subdividing them into elementary visual symptoms. Since visual symptoms of migraine aura are not easy to describe verbally, we developed a collection of images illustrating previously reported elementary visual symptoms. OBJECTIVES: To test a standardised visual migraine aura iconography in a large population of migraine with aura patients and to improve it based on the participants' feedback. METHODS: We created a set of images representing 25 elementary visual symptoms and a web-based survey where participants could report whether they recognised these images as part of their visual aura. Elementary visual symptoms could also be recognised via a corresponding text description or described in a free text by participants. Individuals with migraine aura recruited from four tertiary headache centres (in Switzerland, Denmark, Norway and Italy) were invited to complete the survey. RESULTS: Two hundred and fifteen participants completed the study (78.9% women, median age 36). They recognised a total of 1645 elementary visual symptoms from our predefined list. Of those, 1291 (78.4%) where recognised via standardised iconography images. A new type of elementary visual symptom was reported by one participant. CONCLUSION: Most elementary visual symptoms experienced by participants were recognised via the standardised iconography. This tool can be useful for clinical as well as research purposes.

Retreating migraine patients in the second year with monoclonal antibodies anti-CGRP pathway: the multicenter prospective cohort RE-DO study.

BACKGROUND: The outcome of migraine patients retreated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (anti-CGRP) or its receptor (anti-CGRPr) is not completely known. METHODS: This multicentric prospective observational cohort study assessed monthly migraine days (MMDs), migraine acute medication intake (MAMI), and HIT-6 at baseline, after 90-112 days (Rev-1), after 84-90 days since Rev-1 (Rev-2) and 30 days after the last injection of anti-CGRP/CGRPr mAbs (Year-end), in the first and the second year after a discontinuation period. RESULTS: We enrolled 226 patients (79.6% with chronic migraine; 55.3% on erenumab and 44.7% on galcanezumab or fremanezumab). MMDs, MAMI, and HIT-6-did not differ at the respective first and second-year evaluations in the entire cohort, and comparing anti-CGRP with anti-CGRPr Abs. MMDs (18.1 ± 7.8 vs. 3.4 ± 7.8), MAMI (26.7 ± 28.3 vs.17.7 ± 17.2), and HIT-6 scores (63.1 ± 5.9 vs. 67.1 ± 10.3) were lower in the second year than in the pre-treatment baseline (consistently, p < 0.0001). Second-year baseline MMDs were lower in patients on anti-CGRP mAbs (p = 0.001) and with lower pre-treatment baseline MMDs (p ≤ 0.001). CONCLUSION: Anti-CGRP/CGRPr mAbs are effective in the second as in the first year. The use of anti-CGRP or CGRPr mAbs influenced the second-year baseline MMDs, but their effectiveness did not differ during the two treatment years.

Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study.

BACKGROUND AND PURPOSE: To evaluate the 1-year effectiveness and tolerability of galcanezumab in real life and the prognostic indicators of persistent response. METHODS: High-frequency episodic migraine (HFEM) and chronic migraine (CM) patients treated with galcanezumab who completed a 1-year observation were enrolled. The primary outcomes assessed during the 12 months (V1-V12) were the change in monthly migraine days (MMDs) from baseline and the response rates ≥50% in MMDs (MMD ≥50% RR). The secondary outcomes were changes in pain intensity (numerical rating scale [NRS]) and in monthly acute medication intake (MAMI). RESULTS: We enrolled 191 patients (77.5% CM). Twenty-three patients (12%) dropped out, two for nonserious adverse events. At least 40% of patients took add-on standard preventives from baseline to V12. At V12, MMDs were reduced by 6.0 days in HFEM and by 11.9 days in CM patients (both p < 0.00001); NRS and MAMI were also decreased in both groups (p < 0.00001). One-hundred eight (56.5%) patients presented MMD ≥50% RR for 9 cumulative months (interquartile range=8): we defined this value as the cutoff for a persistent response. Persistent responders were less likely to have a higher body mass index (BMI) (p = 0.007) but more frequently had a good response to triptans (p = 0.005) and MMD ≥50% RR at V1 (p < 0.0000001). Patients without a persistent response were on add-on therapy for longer periods of time (p < 0.001). CONCLUSIONS: Galcanezumab was effective and well-tolerated in the 1-year term, with most patients presenting MMD ≥50% RR for at least 9 months. Triptan response, lower BMI, and MMD ≥50% RR in the first month emerged as predictive factors for a persistent response.

Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience.

OBJECTIVE: To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8-14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4-7 MMDs), and Low-Frequency EM (LFEM, 0-3 MMDs), and its persistence during 1 year of treatment with galcanezumab. METHODS: Consecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12). RESULTS: Of the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age (p = 0.010) and fewer baseline MMDs (p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs (p < 0.000001) while the NRS score reduced by almost 2 points (p < 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients. DISCUSSION: The 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04803513.

Impact of weather and pollution on the rate of cerebrovascular events in a large metropolitan area.

BACKGROUND: Despite mounting evidence, there is uncertainty on the impact of the interplay between weather and pollution features on the risk of acute cerebrovascular events (CVE). We aimed at appraising role of weather and pollution on the daily risk of CVE. METHODS: Anonymized data from a hub CVE center in a large metropolitan area were collected and analyzed according to weather (temperature, pressure, humidity, and rainfall) and pollution (carbon monoxide [CO], nitrogen dioxide [NO2], nitrogen oxides [NOX], ozone [O3], and particulate matter [PM]) on the same and the preceding days. Poisson regression and time series analyses were used to appraise the association between environmental features and daily CVE, distinguishing also several subtypes of events. RESULTS: We included a total of 2534 days, with 1363 days having ≥1 CVE, from 2012 to 2017. Average daily rate was 1.56 (95% confidence interval: 1.49; 1.63) for CVE, with other event rates ranging between 1.42 for stroke and 0.01 for ruptured intracranial aneurysm. Significant associations were found between CVE and temperature, pressure, CO, NO2, NOX, O3, and PM <10 µm (all P<0.05), whereas less stringent associations were found for humidity, rainfall, and PM <2.5 µm. Time series analysis exploring lag suggested that associations were stronger at same-day analysis (lag 0), but even environmental features predating several days or weeks were significantly associated with events. Multivariable analysis suggested that CO (point estimate 1.362 [1.011; 1.836], P=0.042) and NO2 (1.011 [1.005; 1.016], P<0.001) were the strongest independent predictors of CVE. CONCLUSIONS: Environmental features are significantly associated with CVE, even several days before the actual event. Levels of CO and NO2 can be potentially leveraged for population-level interventions to reduce the burden of CVE.

Cluster analysis of weather and pollution features and its role in predicting acute cardiac or cerebrovascular events.

BACKGROUND: Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events. METHODS: Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care centers from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rates of acute cardiac and cerebrovascular events with Poisson models. RESULTS: As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, N.=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, N.=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, N.=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, N.=17, 1.5%). Overall cluster-wise comparisons showed significant differences in adverse cardiac and cerebrovascular events (P<0.001), as well as in cerebrovascular events (P<0.001) and strokes (P=0.001). Between-cluster comparisons showed that cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to cluster 2, cluster 3 and cluster 4 (all P<0.05), as well as AMI in comparison to cluster 3 (P=0.047). In addition, cluster 2 was associated with a higher risk of strokes in comparison to cluster 4 (P=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for cluster 1 and cluster 2. CONCLUSIONS: Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increased risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention.

How does semantic pain and words condition pain perception? A short communication.

INTRODUCTION AND SCOPE: Language is one of the main tools with whom people describe their pain. The semantic value of words plays a fundamental role in the pain perception, intended as a complex process of modulation and processing in the brain. The priming effect is a cognitive process in which a certain stimulus can influence subsequent stimuli. It is therefore plausible that this effect plays a key role in the modulation and perception of pain. This study aimed to investigate the potential relationship between the semantic aspects of language, the priming effect, and the perception of pain. METHODS AND RESULTS: A narrative review of the literature was conducted. Sixteen studies were included and categorized in four groups based on the effect of the verbal suggestion on the experimental acute pain and chronic pain and on the effect of pain-related words in free pain and post-surgical subjects. CONCLUSIONS: There may be a link between language and pain, both at the behavioral and neural level. The processing of semantic information associated with pain influences the pain perception.

A snapshot global survey on side effects of COVID-19 vaccines among healthcare professionals and armed forces with a focus on headache.

BACKGROUND: New messenger RNA (mRNA) and adenovirus-based vaccines (AdV) against Coronavirus disease 2019 (COVID-19) have entered large scale clinical trials. Since healthcare professionals (HCPs) and armed forces personnel (AFP) represent a high-risk category, they act as a suitable target population to investigate vaccine-related side effects, including headache, which has emerged as a common complaint. METHODS: We investigated the side-effects of COVID-19 vaccines among HCPs and AFP through a 38 closed-question international survey. The electronic link was distributed via e-mail or via Whatsapp to more than 500 contacts. Responses to the survey questions were analyzed with bivariate tests. RESULTS: A total of 375 complete surveys have been analyzed. More than 88% received an mRNA vaccine and 11% received AdV first dose. A second dose of mRNA vaccine was administered in 76% of individuals. No severe adverse effects were reported, whereas moderate reactions and those lasting more than 1 day were more common with AdV (P=0.002 and P=0.024 respectively). Headache was commonly reported regardless of the vaccine type, but less frequently, with shorter duration and lower severity that usually experienced by participants, without significant difference irrespective of vaccine type. CONCLUSIONS: Both mRNA and AdV COVID-19 vaccines were safe and well tolerated in a real-life subset of HCPs and AFP subjects.

Experimentally induced spinal nociceptive sensitization increases with migraine frequency: a single-blind controlled study.

The nitric-oxide donor nitroglycerin (NTG) administration induces a facilitation of nociceptive pathways in episodic migraine. This study aims to test the hypothesis that induced spinal sensitization could be more pronounced in patients affected by high-frequency migraine (HF-MIG) with respect to low-frequency migraine (LF-MIG). We enrolled 28 patients with LF-MIG (1-5 migraine days/month), 19 patients with HF-MIG (6-14 migraine days/month), and 21 healthy controls (HCs). Spinal sensitization was evaluated with the neurophysiological recording of the temporal summation threshold (TST) of the nociceptive withdrawal reflex at the lower limb. Temporal summation threshold was recorded at baseline and 30, 60, and 120 minutes after NTG administration (0.9 mg sublingual). Spinal sensitization was detected in LF-MIG at 60 (P = 0.010) and 120 minutes (P = 0.001) and in HF-MIG at 30 (P = 0.008), 60 (P = 0.001), and 120 minutes (P = 0.001) after NTG administration. Temporal summation threshold did not change in HC (P = 0.899). Moreover, TST reduction was more pronounced in HF-MIG with respect to LF-MIG (P = 0.002). The percentage of patients who developed a migraine-like headache after NTG was comparable in the 2 migraine groups (LF-MIG: 53.6%, HF-MIG: 52.6%, P = 0.284), whereas no subjects in the HC group developed a delayed-specific headache. Notably, the latency of headache onset was significantly shorter in the HF-MIG group when compared with the LF-MIG group (P = 0.015). Our data demonstrate a direct relationship between migraine frequency and both neurophysiological and clinical parameters, to suggest an increasing derangement of the nociceptive system control as the disease progresses, probably as a result of the interaction of genetic and environmental factors.

OnabotulinumtoxinA Reduces Temporal Pain Processing at Spinal Level in Patients with Lower Limb Spasticity.

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales (neuropathic pain scale inventory (NPSI), numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity.

Effect of phobic visual stimulation on spinal nociception.

To explore the role of strong negative emotions in spinal nociception, we evaluated the effect of fear-relevant videos of small animals on the nociceptive withdrawal reflex (NWR) and reflex-related pain perception in healthy subjects with a specific phobia of small animals. Twenty healthy subjects with a specific phobia of small animals diagnosed according to DSM-V criteria were included in this study. The NWR was evoked in the lower limb by stimulating the sural nerve and recording EMG activity in the biceps femoris. NWR pain-related perception was quantified on an 11-point numerical rating scale (NRS). Subjects were examined during 4 recording sessions. In the baseline session, no images were projected. In the other sessions, the subjects were invited to watch a video containing either neutral or phobic content. To evaluate neurovegetative responses, we measured heart rate using a pulse oximeter during each recording session. A series of clinical rating scales were administered to subjects to evaluate disgust, fear, and anxiety. The NWR amplitude was significantly increased during the phobic video session and was associated with the fear inventory scale scores. Women showed higher NWR amplitude values during the phobic video session and a lower recovery rate during the after-effect video session than did men. The NWR amplitude and related pain perception were dissociated from each other during the phobic video session, as the NRS score remained unchanged while the NWR increased in amplitude. Emotions induced by the viewing of phobic videos seem to enhance the activation of the spinal circuitries involved in nociception and the withdrawal reaction without interfering with pain processing pathways or dissociating the reflex response from related pain perception. This effect appears to differ by sex, as it was more intense and longer lasting in women than in men. Emotions induced by phobic video viewing increase the alertness devoted to the defensive reaction by emphasizing nociceptive responses independently from pain perception. The NWR may represent an interesting tool for exploring the interaction between strong negative emotions and spinal nociception. A better understanding of this mechanism may be a theoretical prerequisite for the optimization of pain management in several chronic pain syndromes.

The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment.

Background: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. Methods: Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group (n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group (n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS (n = 12) and sham ts-DCS (n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. Results: Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. Conclusions: Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT02331654.

Botulinum toxin A modifies nociceptive withdrawal reflex in subacute stroke patients.

OBJECTIVES: The aims of this study were to evaluate the pattern of the nociceptive withdrawal reflex (NWR) of the upper limb at rest and after injection of Botulinum toxin type A (BoNT-A) in poststroke subacute hemiparetic patients. METHODS: Fourteen patients with poststroke subacute hemiparesis underwent clinical and instrumental evaluation and BoNT-A injection. Painful electrical stimulation was applied to induce the NWR. Baseline EMG activity and NWR recordings (EMG and kinematic response) were performed at T0, one month (T1), and three months (T2) after the BoNT-A injection, as were Modified Ashworth Scale (MAS) and Functional Independence Measure (FIM) scores. RESULTS: Comparison of results at T0, T1, and T2 revealed significant changes in the MAS score for the elbow (p < 0.001) and wrist joints (p < 0.001) and in the FIM score at T0 and T2. BoNT-A injection had a significant effect on both NWR amplitude and baseline EMG activity in the posterior deltoid (PD) and flexor carpi radialis (FCR) muscles as well as in all averaged muscles. Analysis of elbow kinematics before and after treatment revealed that the reflex probability rates were significantly higher at T1 and T2 than at T0. CONCLUSION: Injection of BoNT-A in the subacute phase of stroke can modify both the baseline EMG activity and the NWR-related EMG responses in the upper limb muscles irrespective of the site of injection; furthermore, the reflex-mediated defensive mechanical responses, that is, shoulder extension and abduction and elbow flexion, increased after treatment. BoNT-A injection may be a useful treatment in poststroke spasticity with a potential indirect effect on spinal neurons.

A Novel ATP1A2 Gene Variant Associated With Pure Sporadic Hemiplegic Migraine Improved After Patent Foramen Ovale Closure: A Case Report.

We describe the case of one patient with pure sporadic hemiplegic migraine (SHM) with a novel ATP1A2 gene variant and a large patent foramen ovale (PFO) with atrial septal aneurysm. In hemiplegic migraine (HM), the relationship between incomplete penetrance, environmental triggers, and phenotypic expression is underdetermined. A genetic evaluation of the proband was requested for the HM associated genes and extended to the members of his family. Genetic analysis revealed a never described before ATP1A2 gene mutation, inherited by his father, who never experienced motor aura but only typical visual aura. The proband-but not his father-was also affected by a large PFO with atrial septal aneurysm. SHM patient showed a marked reduction in motor aura episodes per year in the 12 months following the PFO percutaneous closure, followed by a complete remission from attacks at least in the following 24 months. We speculated that as well as incomplete penetrance of the novel mutation and natural history of the disease, an additional pathological condition such as the PFO could contribute to the phenotypical expression in this case of HM.

Trait- and Frequency-Dependent Dysfunctional Habituation to Trigeminal Nociceptive Stimulation in Trigeminal Autonomic Cephalalgias.

We investigated whether the stimulation frequency (SF), the pain phases, and different diagnoses of trigeminal autonomic cephalalgias (TACs) may influence the habituation to pain. We studied the habituation of the nociceptive blink reflex R2 responses at different SFs (.05, .1, .2, .3, .5, and 1 Hz), in 28 episodic cluster headache (ECH) patients, 16 during and 12 outside the bout; they were compared with 16 episodic paroxysmal hemicrania (EPH) during the bout and 21 healthy subjects. We delivered 26 electrical stimuli and subdivided stimuli 2 to 26 in 5 blocks of 5 responses for each SF. Habituation values for each SF were expressed as the percentages of the mean area value of second through fifth blocks with respect to the first one. A significant lower mean percentage decrease of the R2 area across all blocks was found at .2 to 1 Hz SF during ECH, outside of the ECH, and EPH compared with healthy subjects. We showed a common frequency-dependent deficit of habituation of trigeminal nociceptive responses at higher SFs in ECH and EPH patients, independently from the disease phase. This abnormal temporal pattern of pain processing may suggest a trait-dependent dysfunction of some underlying pain-related subcortical structures, rather than a state-dependent functional abnormality due to the recurrence of the headache attacks during the active period. PERSPECTIVE: TACs showed a frequency-related defective habituation of nociceptive trigeminal responses at the higher SFs, irrespectively of the diagnosis and/or the disease phase. We showed that the clinical similarities in the different subtypes of TACs are in parallel with a trait-dependent dysfunction in pain processing.

Pain processing in atypical Parkinsonisms and Parkinson disease: A comparative neurophysiological study.

OBJECTIVE: Pain is a frequent non-motor feature in Parkinsonism but mechanistic data on the alteration of pain processing are insufficient to understand the possible causes and to define specifically-targeted treatments. METHODS: we investigated spinal nociception through the neurophysiological measure of the threshold (TR) of nociceptive withdrawal reflex (NWR) and its temporal summation threshold (TST) comparatively in 12 Progressive Supranuclear Palsy (PSP) subjects, 11 Multiple System Atrophy (MSA) patients, 15 Parkinson's disease (PD) subjects and 24 healthy controls (HC). We also investigated the modulatory effect of L-Dopa in these three parkinsonian groups. RESULTS: We found a significant reduction in the TR of NWR and in the TST of NWR in PSP, MSA and PD patients compared with HC. L-Dopa induced an increase in the TR of NWR in the PSP group while TST of NWR increased in both PSP and PD. CONCLUSIONS: Our neurophysiological findings identify a facilitation of nociceptive processing in PSP that is broadly similar to that observed in MSA and PD. Specific peculiarities have emerged for PSP. SIGNIFICANCE: Our data advance the knowledge of the neurophysiology of nociception in the advanced phases of parkinsonian syndromes and on the role of dopaminergic pathways in the control on pain processing.

Anodal transcranial direct current stimulation over the left temporal pole restores normal visual evoked potential habituation in interictal migraineurs.

BACKGROUND: Neuroimaging data has implicated the temporal pole (TP) in migraine pathophysiology; the density and functional activity of the TP were reported to fluctuate in accordance with the migraine cycle. Yet, the exact link between TP morpho-functional abnormalities and migraine is unknown. Here, we examined whether non-invasive anodal transcranial direct current stimulation (tDCS) ameliorates abnormal interictal multimodal sensory processing in patients with migraine. METHODS: We examined the habituation of visual evoked potentials and median nerve somatosensory evoked potentials (SSEP) before and immediately after 20-min anodal tDCS (2 mA) or sham stimulation delivered over the left TP in interictal migraineurs. RESULTS: Prior to tDCS, interictal migraineurs did not exhibit habituation in response to repetitive visual or somatosensory stimulation. After anodal tDCS but not sham stimulation, migraineurs exhibited normal habituation responses to visual stimulation; however, tDCS had no effect on SSEP habituation in migraineurs. CONCLUSION: Our study shows for the first time that enhancing excitability of the TP with anodal tDCS normalizes abnormal interictal visual information processing in migraineurs. This finding has implications for the role of the TP in migraine, and specifically highlights the ventral stream of the visual pathway as a pathophysiological neural substrate for abnormal visual processing in migraine.

Frequency-Dependent Habituation Deficit of the Nociceptive Blink Reflex in Aura With Migraine Headache. Can Migraine Aura Modulate Trigeminal Excitability?

OBJECTIVE: To study the influence of the migraine aura on the trigeminal nociception, we investigated the habituation of the nociceptive blink reflex (nBR) R2 responses in aura with migraine headache (AwMH) and comparatively in migraine without aura (MWoA) and healthy subjects (HS). BACKGROUND: A clear deficit of habituation in trigeminal nociceptive responses has been documented in MWoA; however, similar data in MWA are lacking. METHODS: Seventeen AwMH, 29 MWoA, and 30 HS were enrolled and a nonrandomized clinical neurophysiological study examining nBR habituation by clinical diagnosis was devised. We delivered a series of 26 electrical stimuli, at different stimulation frequencies (SF) (0.05, 0.1, 0.2, 0.3, 0.5, and 1 Hz), subsequently subdivided in five blocks of five responses for each SF. The mean area values of the second to the fifth block expressed as the percentage of the mean area value of the first block were taken as an index of habituation for each SF. RESULTS: A significant lower mean percentage decrease of the R2 area across all blocks was found at 1, 0.5, 0.3, and 0.2 Hz SF in MWoA and at 0.3 and 0.2 Hz SF in AwMH, when compared to HS. In the most representative fifth block of responses, we found in MWoA vs HS at 1 Hz, 57.0 ± 27.8 vs 30.6 ± 12.0; at 0.5 Hz, 54.8 ± 26.1 vs 32.51 ± 17.7; at 0.3 Hz, 44.7 ± 21.6 vs 27.6 ± 13.2; at 0.2 Hz, 61.3 ± 29.5 vs 32.6 ± 18.0, and in AwMH vs HS at 0.3 Hz, 52.7 ± 24.7 vs 27.6 ± 13.2; at 0.2 Hz, 69.3 ± 38.6 vs 32.6 ± 18.0 as mean ± SD of the R2 area percentage of the first block, respectively. Interestingly, AwMH subjects did not show differences in mean percentage decrease of the R2 area at 1 and 0.5 Hz SF when compared to HS. No differences between groups were found at 0.1 and 0.05 Hz SF. CONCLUSIONS: We demonstrated in AwMH a deficit of habituation of the nBR R2 responses after repeated stimulations, although less pronounced than that observed in MWoA of comparable clinical severity. We hypothesize that AwMH and MWoA share some pathogenetic aspects, and also that migraine aura physiopathology may play a modulating role on the excitability of the nociceptive trigeminal pathways.

Correlation between habituation of visual-evoked potentials and magnetophosphene thresholds in migraine: A case-control study.

INTRODUCTION: In migraine most studies report an interictal deficit of habituation of visual-evoked potentials (VEP-hab) and reduced thresholds for phosphene induction (PT) by transcranial magnetic stimulation (TMS). We searched for a possible correlation between VEP-hab and PT in migraine patients and healthy controls to test whether they reflect the same pathophysiological abnormality. METHODS: We assessed PT and VEP-hab measured as the percentage change of N1/P1 amplitude over six blocks of 100 responses in 15 healthy volunteers (HV) and in 13 episodic migraineurs without aura (MO) between attacks. Results were compared using Mann-Whitney U test. Interrelationships were examined using Spearman's correlation. RESULTS: In MO patients VEP-hab was reduced compared to HV (p = 0.001), while PT were not significantly different between HV and MO. There was no correlation between PT and VEP-hab in either group of participants. CONCLUSIONS: We confirm that in interictal migraine VEP habituation is deficient, but magnetophosphene threshold normal. VEP-hab and PT were not correlated with each other in healthy controls or in migraineurs. This finding suggests that they index different facets of cortical excitability in migraine, i.e. a punctual normal measure of the cortical activation threshold for PT and a dynamic response pattern to repeated stimuli for VEP habituation.