Headaches and facial pain attributed to SARS-CoV-2 infection and vaccination: a systematic review.

BACKGROUND AND PURPOSE: The aim was to provide insights to the characteristics of headache in the context of COVID-19 on behalf of the Headache Scientific Panel and the Neuro-COVID-19 Task Force of the European Academy of Neurology (EAN) and the European Headache Federation (EHF). METHODS: Following the Delphi method the Task Force identified six relevant questions and then conducted a systematic literature review to provide evidence-based answers and suggest specific diagnostic criteria. RESULTS: No data for facial pain were identified in the literature search. (1) Headache incidence during acute COVID-19 varies considerably, with higher prevalence rates in prospective compared to retrospective studies (28.9%-74.6% vs. 6.5%-34.0%). (2) Acute COVID-19 headache is usually bilateral or holocranial and often moderate to severe with throbbing pain quality lasting 2-14 days after first signs of COVID-19; photo-phonophobia, nausea, anosmia and ageusia are common associated features; persistent headache shares similar clinical characteristics. (3) Acute COVID-19 headache is presumably caused by immune-mediated mechanisms that activate the trigeminovascular system. (4) Headache occurs in 13.3%-76.9% following SARS-CoV-2 vaccination and occurs more often amongst women with a pre-existing primary headache; the risk of developing headache is higher with the adenoviral-vector-type vaccines than with other preparations. (5) Headache related to SARS-CoV-2 vaccination is mostly bilateral, and throbbing, pressing, jolting or stabbing. (6) No studies have been conducted investigating the underlying mechanism of headache attributed to SARS-CoV-2 vaccines. CONCLUSION: The results of this joint EAN/EHF initiative provide a framework for a better understanding of headache in the context of SARS-CoV-2 infection and vaccination.

Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls.

BACKGROUND: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity. METHODS: The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18-75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months. RESULTS: 202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders. CONCLUSION: Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case-tailored therapeutic approach.

Exploring Aesthetic Perception in Impaired Aging: A Multimodal Brain-Computer Interface Study.

In the field of neuroscience, brain-computer interfaces (BCIs) are used to connect the human brain with external devices, providing insights into the neural mechanisms underlying cognitive processes, including aesthetic perception. Non-invasive BCIs, such as EEG and fNIRS, are critical for studying central nervous system activity and understanding how individuals with cognitive deficits process and respond to aesthetic stimuli. This study assessed twenty participants who were divided into control and impaired aging (AI) groups based on MMSE scores. EEG and fNIRS were used to measure their neurophysiological responses to aesthetic stimuli that varied in pleasantness and dynamism. Significant differences were identified between the groups in P300 amplitude and late positive potential (LPP), with controls showing greater reactivity. AI subjects showed an increase in oxyhemoglobin in response to pleasurable stimuli, suggesting hemodynamic compensation. This study highlights the effectiveness of multimodal BCIs in identifying the neural basis of aesthetic appreciation and impaired aging. Despite its limitations, such as sample size and the subjective nature of aesthetic appreciation, this research lays the groundwork for cognitive rehabilitation tailored to aesthetic perception, improving the comprehension of cognitive disorders through integrated BCI methodologies.

Galcanezumab treatment changes visual related EEG connectivity patterns in migraine patients.

BACKGROUND: Monoclonal antibodies against calcitonin gene-related peptides (CGRP) are innovative therapies for migraine treatment. Although they are clinically effective, how anti-CGRP treatment reduces migraine attacks still remains unclear. OBJECTIVE: In this observational case-control study, we aimed to apply graph theory to EEG data from 20 migraine patients and 10 controls to investigate the effects of 3 months of galcanezumab on brain connectivity. METHODS: We analyzed EEG rhythms during black-white pattern reversal stimulation with 0.5 cycle per degree spatial frequency before (T0) galcanezumab injection, as well as after 3 months (T2). EEG recordings made 1 hour after galcanezumab administration served as the control session (T1). Patients' connectivity patterns obtained at T0, T1 and T2 were compared with normal controls. RESULTS: We found that galcanezumab increased network integration (with a 5% significance level corrected with the false discovery rate), changing the intensity of connections between the occipital through the frontal areas. At 3 months follow up, patients with persistent high headache intensity had a minor effect on the strength of connections (evaluated using Kendall's rank correlation test and p < 0.05). CONCLUSIONS: The potent anti-nociceptive action that galcanezumab exerts at a peripheral level could restore cortical connections and possibly factors predisposing to attack onset.

Outcome of small fibre pathology in fibromyalgia: a real life longitudinal observational study.

OBJECTIVES: Small fibre pathology is frequently described in fibromyalgia (FM), but its evolution and its role in clinical outcome of the disease are unclear. This longitudinal observational real-life study aimed to monitor the evolution of skin nerve fibre density in FM, in view of the clinical data. METHODS: Sixty-two FM patients were controlled by means of skin biopsy and clinical assessment after 18 months of follow-up. RESULTS: At T0 intraepidermal nerve fibre density (IENFD) was normal in 10 patients, reduced at thigh-proximal-site in 46 cases and decreased at proximal and foot-distal-site in 6 patients. At follow up-T1-the IENFD was unchanged, while Brief Pain Inventory-BPI-pain sub score, DN4 and fatigue were improved. Reduced IENFD at proximal and distal sites, together with fatigue and BPI-motor and work sub scores were predictors of more severe disability measured with Fibromyalgia Impact Questionnaire (FIQ) at T1. Reduced IENFD influenced a minor effect of drugs-antiepileptics and/or antidepressants, and physical exercise on fatigue. CONCLUSIONS: Small fibre impairment seems stable in medium term in FM. A possible influence of small fibre dysfunction on motor performance could have a role in FM evolution. The beneficial effect of physical exercise could be limited in patients with reduced IENFD.

A multicomponent physical activity home-based intervention for fibromyalgia patients: effects on clinical and skin biopsy features.

OBJECTIVES: Adapted physical activity (APA) has been recommended for fibromyalgia (FM) treatment as an essential component of a biopsychosocial therapeutic approach for patients. Previous studies report that aerobic and resistance training are the most effective programs in improving the quality of life and psycho-physical well-being. Patients with FM are frequently affected by an impairment of small fibers innervation, which is evident in the proximal somatic districts. Therefore, this pilot randomised controlled not pharmacological trial aimed to investigate if a 12-week home-based multicomponent (aerobic and resistance training and mobility) physical activity (PA) intervention was effective in improving pain perception, FM-related disability, and IntraEpidermal Nerve Fibers Density (IENFD) in adult FM patients. METHODS: Thirty-four female subjects with a fibromyalgia diagnosis (51.5±11.88 years) were randomly assigned to an experimental group (n=17) that received a supervised home-based multicomponent PA intervention twice a week and a control group (n=17) that received a generic program of aerobic exercise. Skin biopsy was performed before the physical program and after 18 months with constant execution of the supervised PA intervention or generic aerobic exercise. Both groups assumed pharmacological treatment with duloxetine and/or pregabalin. RESULTS: We found that the group performing physical activity in a supervised and regular way showed a significant improvement in the Fibromyalgia-linked invalidity questionnaire (FIQ) as well as epidermal fibers density at proximal and distal sites. CONCLUSIONS: Physical activity could improve FM outcomes, with a possible beneficial impact on peripheral factors contributing to pain-related disability.

The puzzle of fibromyalgia between central sensitization syndrome and small fiber neuropathy: a narrative review on neurophysiological and morphological evidence.

Fibromyalgia (FM) is a condition characterized by chronic widespread pain whose pathogenesis is still not fully defined. Evidence based on structural and functional neuroimaging methods, electrophysiological, and morphological - skin biopsy - features demonstrated a central and peripheral nervous system involvement. A dysfunction in nociceptive inputs processing at the central level was highlighted as the primary cause of FM, but other data coming from different laboratories contributed to emphasize again the peripheral origin of FM. In fact, small fibers neuropathy (SFN) was observed in a large number of patients submitted to skin biopsy. The complex interaction between central and peripheral factors is opening a new scenario about the management of this neurological disorder. Whether proximal SFN is an initiating event leading to FM or is the consequence of stress-related insular hyper excitability remains unclear. Mild sufferance of peripheral afferents could function as a trigger for an exaggerated response of the so-called "salience matrix" in predisposed individuals. On the other side, the intriguing hypothesis rising from animal models could indicate that the cortical hyper function could cause peripheral small afferent damage. The research should go on the genetic origin of such peripheral and central abnormalities, the acquired facilitating factors, and the presence of different phenotypes in order to search for efficacious treatments, which are still lacking.

Central effects of galcanezumab in migraine: a pilot study on Steady State Visual Evoked Potentials and occipital hemodynamic response in migraine patients.

BACKGROUND: The discovery of the prominent action of Calcitonin Gene Related Peptide -CGRP- on trigeminal afferents and meningeal vessels, opened a new era in migraine treatment. However, how the block of nociceptive afferents could act on central mechanisms of migraine is still not clear. In this pilot study we aimed to test the effect of 3 months Galcanezumab (CGA) therapy on occipital visual reactivity in migraine patients, using the Steady State Visual Evoked Potentials-SSVEPs and Functional Near Infrared Spectroscopy -fNIRS. METHOD: Thirteen migraine patients underwent clinical and neurophysiological examination in basal condition (T0), 1 h after GCA injection (T1) and after 3 months of GCA treatment (T2). Ten healthy volunteers were also evaluated. RESULTS: At T2, there was a reduction of headache frequency and disability. At T2, the EEG power significantly diminished as compared to T0 and T1 at occipital sites, and the topographical analysis confirmed a restoration of SSVEPs within normal values. The Oxyhemoglobin levels in occipital cortex, which were basically increased during visual stimulation in migraine patients, reverted to normal values at T2. CONCLUSIONS: The present pilot study indicates that Galcanezumab could act on cortical targets located beyond the pain network, restoring the abnormal occipital reactivity. This effect could indicate the possible disease modifying properties of CGRP related monoclonal antibodies.

Effect of single dose Erenumab on cortical responses evoked by cutaneous a-delta fibers: A pilot study in migraine patients.

BACKGROUND: Erenumab is a monoclonal antibody against calcitonin gene-related peptide receptors, which showed efficacy in migraine attack prevention. The aims of the present pilot study were to i) evaluate the effect of single dose of Erenumab 70 mg on laser evoked potentials from trigeminal and brachial stimulation in a cohort of migraine patients; ii) correlate the neurophysiological changes with clinical outcome after 3 months' treatment. METHODS: Laser evoked potentials were recorded by 61 electroencephalogram channels before (T0), 1 h (T1) and 7 days after (T2) Erenumab 70 mg injection, stimulating the left and right forehead and the right hand. Laser evoked potential control 1 h after the injection served as placebo session. RESULTS: Seventeen migraine patients were evaluated. The N1 and N2 component obtained from the right and left trigeminal stimulation diminished in amplitude at T2, compared to T0 and T1 conditions. N2 habituation reduction slightly recovered at T2. Laser evoked potential changes did not correlate with clinical improvement after 3 months of Erenumab treatment. CONCLUSIONS: A single dose of Erenumab has a mild inhibitory effect on cortical responses evoked from trigeminal cutaneous a-delta fibers. Though this phenomenon was not predictive of the clinical outcome, it confirms a wide representation of calcitonin gene-related peptide receptors on trigeminal afferents.

Osmophobia in primary headache patients: associated symptoms and response to preventive treatments.

BACKGROUND: Osmophobia, is common among primary headaches, with prevalence of migraine. The study aimed to evaluate prevalence and clinical characteristics of patients with osmophobia in a cohort of primary headache patients selected at a tertiary headache center. The second aim was to verify the possible predicting role of osmophobia in preventive treatment response in a sub cohort of migraine patients. METHODS: This was an observational retrospective cohort study based on data collected in a tertiary headache center. We selected patients aged 18-65 years, diagnosed as migraine without aura (MO), migraine with aura (MA) or Chronic Migraine (CM), Tension-Type Headache (TTH); and Cluster Headache (CH). We also selected a sub-cohort of migraine patients who were prescribed preventive treatment, according to Italian Guidelines, visited after 3 months follow up. Patients were considered osmophobic, if reported this symptom in at least the 20% of headache episodes. Other considered variables were: headache frequeny, the migraine disability assessment (MIDAS), Allodynia Symptom Checklist, Self-rating Depression scale, Self-rating Anxiety scale, Pain intensity evaluated by Numerical Rating Scale-NRS- form 0 to 10. RESULTS: The 37,9% of patients reported osmophobia (444 patients with osmophobia, 726 without osmophobia). Osmophobia prevailed in patients with the different migraine subtypes, and was absent in patients with episodic tension type headache and cluster headache (chi square 68.7 DF 7 p < 0.0001). Headache patients with osmophobia, presented with longer hedache duration (F 4.91 p 0.027; more severe anxiety (F 7.56 0.007), depression (F 5.3 p 0.019), allodynia (F 6 p 0.014), headache intensity (F 8.67 p 0.003). Tension type headache patients with osmophobia (n° 21), presented with more frequent headache and anxiety. A total of 711 migraine patients was visited after 3 months treatment. The change of main migraine features was similar between patients with and without osmophobia. CONCLUSIONS: While the present study confirmed prevalence of osmophobia in migraine patients, it also indicated its presence among chronic tension type headache cases, marking those with chronic headache and anxiety. Osmophobia was associated to symptoms of central sensitization, as allodynia. It was not relevant to predict migraine evolution after first line preventive approach.

Failure of preventive treatments in migraine: an observational retrospective study in a tertiary headache center.

BACKGROUND: Although the criteria for acute migraine treatment and prevention have been well described, there are still unmet needs, general underuse and low benefits of preventive drugs. The aim of the present study was to retrospectively observe the short-term effect of preventive treatment in a cohort of migraine patients attending a tertiary headache center, using data from electronic medical records. METHODS: This was an observational retrospective cohort study based on data collected in a tertiary headache center. Data were extracted from an electronic dataset collected from January 2009 to December 2019. The main selection criteria were as follows: age of 18-75 years; diagnosis of migraine without aura (MO), migraine with aura (MA) or chronic migraine (CM); a control visit 3 months after the first access; and prescription of preventive treatment with level of evidence 1 as reported by Italian guidelines. As the primary outcome, we considered the change in the frequency of headache at the follow-up visit. Then, as secondary outcome measures, we used disability scores, intensity of headache, and allodynia. As predictive factors, we considered age, migraine duration, sex, headache frequency, allodynia, anxiety and depression at baseline, and comorbidity with fibromyalgia. RESULTS: Among the 6430 patients screened, 2800 met the selection criteria, 1800 returned to the follow-up visit, 550 withdrew because of adverse events, and 1100 were included the analysis. One hundred thirty-four patients had a frequency reduction of 50% or more. Flunarizine was used for less severe migraine, with a better effect compared to those of other drugs (odds ratio: 1.48; p: 0.022). Low headache frequency and absent or mild allodynia predicted a better outcome. CONCLUSIONS: The mild effect of preventive drugs on migraine features and even the number of patients who were lost to follow-up or dropped out because of adverse events confirm that in severe and chronic patients, the first line of prevention can only delay a more focused therapeutic approach.

Pearl and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part II.

This review focuses on new and/or less standardized event-related potentials methods, in order to improve their knowledge for future clinical applications. The olfactory event-related potentials (OERPs) assess the olfactory functions in time domain, with potential utility in anosmia and degenerative diseases. The transcranial magnetic stimulation-electroencephalography (TMS-EEG) could support the investigation of the intracerebral connections with very high temporal discrimination. Its application in the diagnosis of disorders of consciousness has achieved recent confirmation. Magnetoencephalography (MEG) and event-related fields (ERF) could improve spatial accuracy of scalp signals, with potential large application in pre-surgical study of epileptic patients. Although these techniques have methodological limits, such as high inter- and intraindividual variability and high costs, their diffusion among researchers and clinicians is hopeful, pending their standardization.

Pearls and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part I.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Effects of Botulinum Toxin A on Allodynia in Chronic Migraine: An Observational Open-Label Two-Year Study.

BACKGROUND: Onabotulinumtoxin A (OBT-A) is a treatment option for chronic migraine (CM), though the possible effect on central sensitization and allodynia is still unknown. AIMS: The present study aimed to evaluate (1) the long-term outcome of allodynia in a group of CM treated with OBT-A (2) if the presence and severity of allodynia could predict the long-term effect of OBT-A (3) if the improvement of allodynia, could contribute to the clinical efficacy of OBT-A. METHODS: This was an observational, open-label, cohort study conducted on 99 CM patients treated for 1 year and 44 patients treated for 2 years with periodic OBT-A 155-195 U injections. In basal condition (T0), after 1 year (T1) and 2 years (T2) treatment, allodynia, migraine disability, and headache frequency were the main variables. Anxiety, depression and sleep deprivation were also considered potentially correlated factors to allodynia. RESULTS: Allodynia decreased after 1 year (Student t test p = 0.0001), and decreased further after the second year of treatment (p = 0.015). There was a relationship between allodynia severity at T0 and reduced headache frequency change at T1 (r = 0.22) and T2 (r = 0.37). The effect of OBT-A on allodynia correlated with the reduction of MIDAS score after 1 year (r = 0.4) and 2 years (r = 0. 63) of treatment. CONCLUSIONS: OBT-A seems to have an effect on central sensitization, expressed by allodynia. This action could be exerted by modulating nociceptive transmission, and reducing the global burden of migraine. Patients with more severe allodynia display a limited long-term effect on headache frequency. The modulation of central sensitization could reduce migraine disability, in spite of the persistence of frequent headache.

Correction to: Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial.

Following publication of the original article [1], the authors notified us that a part of the Figure 3 legend was omitted during proofing stage.

Effects of external trigeminal nerve stimulation (eTNS) on laser evoked cortical potentials (LEP): A pilot study in migraine patients and controls.

Background Transcutaneous external supraorbital nerve stimulation has emerged as a treatment option for primary headache disorders, though its action mechanism is still unclear. Study aim In this randomized, sham-controlled pilot study we aimed to test the effects of a single external transcutaneous nerve stimulation session on pain perception and cortical responses induced by painful laser stimuli delivered to the right forehead and the right hand in a cohort of migraine without aura patients and healthy controls. Methods Seventeen migraine without aura patients and 21 age- and sex-matched controls were selected and randomly assigned to a real or sham external transcutaneous nerve stimulation single stimulation session. The external transcutaneous nerve stimulation was delivered with a self-adhesive electrode placed on the forehead and generating a 60 Hz pulse at 16 mA intensity for 20 minutes. For sham stimulation, we used 2 mA intensity. Laser evoked responses were recorded from 21 scalp electrodes in basal condition (T0), during external transcutaneous nerve stimulation and sham stimulation (T1), and immediately after these (T2). The laser evoked responses were analyzed by LORETA software. Results The real external transcutaneous nerve stimulation reduced the trigeminal N2P2 amplitude in migraine and control groups significantly in respect to placebo. The real stimulation was associated with lower activity in the anterior cingulate cortex under trigeminal laser stimuli. The pattern of LEP-reduced habituation was reverted by real and sham transcutaneous stimulation in migraine patients. Conclusions The present results could suggest that the external transcutaneous nerve stimulation may interfere with the threshold and the extent of trigeminal system activation, with a mechanism of potential utility in the resolution and prevention of migraine attacks.

Circadian rhythms of migraine attacks in episodic and chronic patients: a cross sectional study in a headache center population.

BACKGROUND: Migraine is considered a disease with diurnal and 24 h pattern, though the existence of a prevalent circadian rhythm associated to migraine frequency and severity is still not clear. This observational cross-sectional study aimed to: 1. Assess the circadian rhythm of migraine attacks onset in a large patients' population selected in a headache center and including episodic and chronic migraine 2. Analyze the principal characteristic of the different onset time groups 3. Verify if migraine features, particularly those associated to chronic and disabling migraine, could be discriminant factors for time of onset group. METHODS: We selected 786 consecutive migraine outpatients, who correctly completed the headache diaries for 3 consecutive months and who fulfilled the diagnosis of migraine without aura-MO, migraine with typical aura alone or associated to migraine without aura - MO/MA and chronic migraine - CM. For the time of headache onset, we considered four time slots, from 6 to 12 am (morning), from 1 to 6 pm (afternoon), from 7 to 11 pm (evening), from 12 pm to 5 am (night), and an additional category named "any time". Each time slot included the 60 min preceding the next one (e.g. an onset at 12.30 am was included in 6-12 am time slot). We evaluated in all patients the pericranial tenderness, anxiety and depression tracts, headache-related disability, sleep features, quality of life, allodynia and fatigue. RESULTS: We scored a total of 16,578 attacks, distributed in the entire day. The most of patients, including CM, satisfied the criteria for the "any time" onset. Night onset was significantly less represented in the MA/MO group. Patients with prevalent night onset were significantly older, with longer migraine history and shorter sleep duration. Age and illness duration were the variables discriminating the different onset time groups. CONCLUSIONS: The most of migraine patients do not report a specific circadian profile of attacks occurrence. Frequent migraine, severe disability, psychopathological tracts as well as central sensitization signs, do not match with a specific circadian rhythm of attacks onset. Night onset migraine seems to be an age related feature, emerging in the course of the disease.

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial.

BACKGROUND: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. METHODS: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. RESULTS: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). CONCLUSIONS: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02686034 .

Correction to: Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial.

Following publication of the original article [1], the authors notified us o that the Table 1 citation within the legend was not presented as initially requested.