Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Decoding pain through facial expressions: a study of patients with migraine.

BACKGROUND: The present study used the Facial Action Coding System (FACS) to analyse changes in facial activities in individuals with migraine during resting conditions to determine the potential of facial expressions to convey information about pain during headache episodes. METHODS: Facial activity was recorded in calm and resting conditions by using a camera for both healthy controls (HC) and patients with episodic migraine (EM) and chronic migraine (CM). The FACS was employed to analyse the collected facial images, and intensity scores for each of the 20 action units (AUs) representing expressions were generated. The groups and headache pain conditions were then examined for each AU. RESULTS: The study involved 304 participants, that is, 46 HCs, 174 patients with EM, and 84 patients with CM. Elevated headache pain levels were associated with increased lid tightener activity and reduced mouth stretch. In the CM group, moderate to severe headache attacks exhibited decreased activation in the mouth stretch, alongside increased activation in the lid tightener, nose wrinkle, and cheek raiser, compared to mild headache attacks (all corrected p < 0.05). Notably, lid tightener activation was positively correlated with the Numeric Rating Scale (NRS) level of headache (p = 0.012). Moreover, the lip corner depressor was identified to be indicative of emotional depression severity (p < 0.001). CONCLUSION: Facial expressions, particularly lid tightener actions, served as inherent indicators of headache intensity in individuals with migraine, even during resting conditions. This indicates that the proposed approach holds promise for providing a subjective evaluation of headaches, offering the benefits of real-time assessment and convenience for patients with migraine.

Electrophysiological findings in migraine may reflect abnormal synaptic plasticity mechanisms: A narrative review.

BACKGROUND: The cyclical brain disorder of sensory processing accompanying migraine phases lacks an explanatory unified theory. METHODS: We searched Pubmed for non-invasive neurophysiological studies on migraine and related conditions using transcranial magnetic stimulation, electroencephalography, visual and somatosensory evoked potentials. We summarized the literature, reviewed methods, and proposed a unified theory for the pathophysiology of electrophysiological abnormalities underlying migraine recurrence. RESULTS: All electrophysiological modalities have determined specific changes in brain dynamics across the different phases of the migraine cycle. Transcranial magnetic stimulation studies show unbalanced recruitment of inhibitory and excitatory circuits, more consistently in aura, which ultimately results in a substantially distorted response to neuromodulation protocols. Electroencephalography investigations highlight a steady pattern of reduced alpha and increased slow rhythms, largely located in posterior brain regions, which tends to normalize closer to the attacks. Finally, non-painful evoked potentials suggest dysfunctions in habituation mechanisms of sensory cortices that revert during ictal phases. CONCLUSION: Electrophysiology shows dynamic and recurrent functional alterations within the brainstem-thalamus-cortex loop varies continuously and recurrently in migraineurs. Given the central role of these structures in the selection, elaboration, and learning of sensory information, these functional alterations suggest chronic, probably genetically determined dysfunctions of the synaptic short- and long-term learning mechanisms.

Identification of patients with chronic migraine by using sensory-evoked oscillations from the electroencephalogram classifier.

BACKGROUND: To examine whether the modulating evoked cortical oscillations could be brain signatures among patients with chronic migraine, we investigated cortical modulation using an electroencephalogram with machine learning techniques. METHODS: We directly record evoked electroencephalogram activity during nonpainful, painful, and repetitive painful electrical stimulation tasks. Cortical modulation for experimental pain and habituation processing was analyzed and used to differentiate patients with chronic migraine from healthy controls using a validated machine-learning model. RESULTS: This study included 80 participants: 40 healthy controls and 40 patients with chronic migraine. Evoked somatosensory oscillations were dominant in the alpha band. Longer latency (nonpainful and repetitive painful) and augmented power (nonpainful and repetitive painful) were present among patients with chronic migraine. However, for painful tasks, alpha increases were observed among healthy controls. The oscillatory activity ratios between repetitive painful and painful tasks represented the frequency modulation and power habituation among healthy controls, respectively, but not among patients with chronic migraine. The classification models with oscillatory features exhibited high performance in differentiating patients with chronic migraine from healthy controls. CONCLUSION: Altered oscillatory characteristics of sensory processing and cortical modulation reflected the neuropathology of patients with chronic migraine. These characteristics can be reliably used to identify patients with chronic migraine using a machine-learning approach.

The SIH-EBP Score: A grading scale to predict the response to the first epidural blood patch in spontaneous intracranial hypotension.

BACKGROUND: To develop and validate an easy-to-use scoring system to predict the response to the first epidural blood patching in patients with spontaneous intracranial hypotension. METHODS: This study recruited consecutive patients with spontaneous intracranial hypotension receiving epidural blood patching in a tertiary medical center, which were chronologically divided into a derivation cohort and a validation cohort. In the derivation cohort, factors associated with the first epidural blood patching response were identified by using multivariable logistic regression modeling. A scoring system was developed, and the cutoff score was determined by using the receiver operating characteristic curve. The findings were verified in an independent validation cohort. RESULTS: The study involved 280 patients in the derivation cohort and 78 patients in the validation cohort. The spontaneous intracranial hypotension-epidural blood patching score (range 0-5) included two clinical variables (sex and age) and two radiological variables (midbrain-pons angle and anterior epidural cerebrospinal fluid collections). A score of ≥3 was predictive of the first epidural blood patching response, which was consistent in the validation cohort. Overall, patients who scored ≥3 were more likely to respond to the first epidural blood patching (odds ratio = 10.3). CONCLUSION: For patients with spontaneous intracranial hypotension-epidural blood patching score ≥3, it is prudent to attempt at least one targeted epidural blood patching before considering more invasive interventions.

Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study.

AIM: This study aimed to investigate the extent of autonomic nervous system dysfunction in patients with chronic migraine using heart rate variability analysis. In addition, we explored the potential association between heart rate variability and treatment outcomes in patients receiving preventive treatment. METHODS: In this cross-sectional and prospective study, we compared heart rate variability profiles in 81 preventive-naïve chronic migraine patients and 58 healthy controls. In addition, treatment responses of patients, who received a 12-week treatment with flunarizine, were assessed in relation to baseline heart rate variability. RESULTS: We observed that chronic migraine patients had a reduced heart rate variability, signifying autonomic dysfunction in comparison to healthy controls. Furthermore, patients presenting normal heart rate variability, characterized by a standard deviation exceeding 30 milliseconds in normal-to-normal RR intervals, experienced a superior response to flunarizine treatment. This improvement was exemplified by a significantly larger reduction in monthly headache days for patients with higher heart rate variability compared to those with lower heart rate variability: -9.7 (5.9) vs. -6.2 (6.0) days (p = .026). CONCLUSIONS: Autonomic dysfunction occurs in chronic migraine as evaluated by heart rate variability. A preserved function is associated with a better treatment outcome to flunarizine.Trial registration: Neurologic Signatures of Chronic Pain Disorders, NCT02747940. Registered 22 April 2016, https://clinicaltrials.gov/ct2/show/NCT02747940.

Brain morphometry changes with fatigue severity in fibromyalgia.

OBJECTIVES: This study investigated brain morphometry changes associated with fatigue severity in fibromyalgia (FM). METHODS: Clinical profiles and brain-MRI data were collected in patients with FM. Patients were divided into three groups based on their fatigue severity. Using voxel-based morphometry analysis and trend analysis, neural substrates showing volumetric changes associated with fatigue severity across the three groups were identified. Their seed-to-voxel structural covariance (SC) networks with the whole brain were studied in distribution and strength. RESULTS: Among the 138 enrolled patients with FM, 23, 57, and 58 were categorised into the mild, moderate, and severe fatigue groups, respectively. The number of musculoskeletal pain regions and intensity of pain were not associated with fatigue severity, but somatic symptoms and psychiatric distress, including waking unrefreshed, depression, and anxiety, were associated with fatigue severity. After adjusting for anxiety and depression, decreased bilateral thalamic volumes were associated with higher fatigue severity. The SC distributions of the thalamic seed were more widespread to the frontal, parietal, subcortical, and limbic regions in patients with higher fatigue severity. In addition, increased right inferior temporal cortex volumes were associated with higher fatigue severity. The SC distributions of the right inferior temporal seed were more over the temporal cortex and the SC strengths of the seed were higher with the bilateral occipital cortex in patients with higher fatigue severity. CONCLUSIONS: The thalamus and the right inferior temporal cortex are implicated in the manifestation of fatigue severity in FM. Future therapeutic strategies targeting these regions are worthy of investigation.

Sphenopalatine ganglion volumetry in episodic cluster headache: from symptom laterality to cranial autonomic symptoms.

BACKGROUND: Sphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles. METHODS: We prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0-5) were recorded to analyze their association with SPG volume. RESULTS: The inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84-0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] µL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] µL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066). CONCLUSIONS: This proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH.

Sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache.

OBJECTIVE: The present study aimed to compare sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache (MOH). METHODS: Consecutive patients with newly diagnosed chronic migraine (CM) with and without MOH based on the Third Edition of International Classification of Headache Disorders (ICHD-3) were enrolled prospectively from the headache clinic of a tertiary medical center. Demographics and clinical profiles were collected by using a questionnaire, which included current use of tobacco, alcohol, and caffeinated beverages, the Leeds Dependence Questionnaire (LDQ), the Severity of Dependence Scale (SDS), the Headache Impact Test-6 (HIT-6), and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 1419 CM patients (1135F/284 M, mean age 41.7 ± 13.9 years) were recruited, including 799 with MOH (640F/159 M, mean age 42.5 ± 13.2 years) (56.3%). Smoking was associated with an increased risk for MOH in men (odds ratio [OR] = 3.60 [95% confidence interval = 1.73-7.50], p = 0.001), but not in women (OR = 1.34 [0.88-2.04], p = 0.171) (p = 0.021 for interaction). Hypnotic use ≥ 3 days/week was a risk factor for MOH (OR = 2.55 [95% confidence interval = 2.00-3.24], p < 0.001), regardless of sex. By using receiver operating characteristics (ROC) curves, the cutoff scores of the LDQ for MOH were determined at 7 for women and 6 for men, and those for the SDS were 5 and 4, respectively (area under curve all ≥ 0.83). Among patients with MOH, the male sex was associated with a shorter latency between migraine onset and CM onset (12.9 ± 11.1 vs. 15.4 ± 11.5 years, p = 0.008), despite less average headache intensity (6.7 ± 1.9 vs. 7.2 ± 1.9, p = 0.005), functional impacts (HIT-6: 63.4 ± 8.3 vs. 65.1 ± 8.0, p = 0.009), and sleep disturbances (PSQI: 10.9 ± 4.4 vs. 12.2 ± 4.3, p = 0.001). CONCLUSIONS: The current study identified an association between smoking and MOH in men, as well as sex-specific cutoffs of the LDQ and the SDS, for MOH. MOH was characterized by a shorter latency between migraine onset and CM onset in men and a more severe phenotype in women. Sex should be considered as an important factor in the evaluation of MOH.

Characteristic oscillatory brain networks for predicting patients with chronic migraine.

To determine specific resting-state network patterns underlying alterations in chronic migraine, we employed oscillatory connectivity and machine learning techniques to distinguish patients with chronic migraine from healthy controls and patients with other pain disorders. This cross-sectional study included 350 participants (70 healthy controls, 100 patients with chronic migraine, 40 patients with chronic migraine with comorbid fibromyalgia, 35 patients with fibromyalgia, 30 patients with chronic tension-type headache, and 75 patients with episodic migraine). We collected resting-state magnetoencephalographic data for analysis. Source-based oscillatory connectivity within each network, including the pain-related network, default mode network, sensorimotor network, visual network, and insula to default mode network, was examined to determine intrinsic connectivity across a frequency range of 1-40 Hz. Features were extracted to establish and validate classification models constructed using machine learning algorithms. The findings indicated that oscillatory connectivity revealed brain network abnormalities in patients with chronic migraine compared with healthy controls, and that oscillatory connectivity exhibited distinct patterns between various pain disorders. After the incorporation of network features, the best classification model demonstrated excellent performance in distinguishing patients with chronic migraine from healthy controls, achieving high accuracy on both training and testing datasets (accuracy > 92.6% and area under the curve > 0.93). Moreover, in validation tests, classification models exhibited high accuracy in discriminating patients with chronic migraine from all other groups of patients (accuracy > 75.7% and area under the curve > 0.8). In conclusion, oscillatory synchrony within the pain-related network and default mode network corresponded to altered neurophysiological processes in patients with chronic migraine. Thus, these networks can serve as pivotal signatures in the model for identifying patients with chronic migraine, providing reliable and generalisable results. This approach may facilitate the objective and individualised diagnosis of migraine.

Mutation screening and association analysis of NOTCH3 p.R544C in patients with migraine with or without aura.

BACKGROUND: The role of the NOTCH3 p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown. METHODS: Migraine patients (n = 2,884) (2,279F/605M, mean age 38.8 ± 11.7 years), including 324 (11.2%) with migraine with aura, were prospectively enrolled by headache specialists according to the International Classification of Headache Disorders criteria. These patients and 3,502 population controls free of stroke, dementia, and headache were genotyped for NOTCH3 p.R544C by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Clinical manifestations and brain magnetic resonance images were examined and compared between migraine patients with and without NOTCH3 p.R544C. RESULTS: Thirty-two migraine patients (1.1%) and 36 controls (1.0%) harbored the p.R544C variant, and the percentages were comparable among migraine patients without and with aura, and controls (1.2%, vs. 0.6% vs. 1.0%, p = 0.625). Overall, migraine patients with and without the p.R544C variant had similar percentages of migraine with aura, headache characteristics, frequencies and disabilities. However, those with p.R544C were less likely to have pulsatile headaches (50.0% vs. 68.2%, p = 0.028), and more likely to have moderate to severe white matter hyperintensities in the external capsule (18.8% vs. 1.2%, p = 0.006) and anterior temporal lobe (12.5% vs. 0%, p = 0.008). CONCLUSIONS: Our findings suggest that NOTCH3 p.R544C does not increase the risk of migraine with aura, or migraine as a whole, and generally does not alter clinical manifestations of migraine. The role of NOTCH3 variants, as well as potential influences from ethnicity or modifier genes, in migraine needs to be further clarified.

Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study.

BACKGROUND: We aimed to assess the differences in quantitative sensory testing between chronic migraine and healthy controls and to explore the association between pain sensitivities and outcomes in chronic migraine following preventive treatment. METHODS: In this prospective open-label study, preventive-naïve chronic migraine and healthy controls were recruited, and cold, heat, mechanical punctate, and pressure pain thresholds over the dermatomes of first branch of trigeminal nerve and first thoracic nerve were measured by quantitative sensory testing at baseline. Chronic migraines were treated with flunarizine and treatment response was defined as ≥50% reduction in the number of monthly headache days over the 12-week treatment period. RESULTS: Eighty-four chronic migraines and fifty age-and-sex-matched healthy controls were included in the analysis. The chronic migraine had higher cold pain thresholds over the dermatomes of the first branch of trigeminal nerve and the first thoracic nerve (p < 0.001 and < 0.001), lower pressure pain thresholds over the dermatomes of the first thoracic nerve (p = 0.003), heat pain thresholds over the dermatomes of the first branch of the trigeminal nerve and the first thoracic nerve (p < 0.001 and p = 0.015) than healthy controls. After treatment, 24/84 chronic migraine had treatment response. The responders with relatively normal pain sensitivity had higher heat pain thresholds over the dermatome of the first branch of the trigeminal nerve (p = 0.002), mechanical punctate pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.023), and pressure pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.026) than the hypersensitive non-responders. Decision tree analysis showed that patients with mechanical punctate pain threshold over the dermatomes of the first branch of the trigeminal nerve > 158 g (p = 0.020) or heat pain threshold over the dermatome of the first branch of the trigeminal nerve > 44.9°C (p = 0.002) were more likely to be responders. CONCLUSIONS: Chronic migraine were generally more sensitive compared to healthy controls. Preventive treatment with flunarizine should be recommended particularly for chronic migraine who have relatively normal sensitivity to mechanical punctate or heat pain.Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT02747940).

Sex-related differences in cluster headache: A hospital-based study in Taiwan.

OBJECTIVES: To compare the clinical profiles between male and female cluster headache patients from a large cohort. METHODS: This hospital-based study enrolled patients diagnosed with cluster headache between 1997 to 2021. Participants completed structured questionnaires collecting information on demographics, clinical profiles, and quality of life. Treatment regimens and effectiveness were determined through medical chart review. All variables were compared between the sexes. RESULTS: In total, 798 patients (M/F:659/139) were enrolled. The male-to-female ratio was 4.7:1 for the full study period, but it declined from 5.2:1 to 4.3:1 for patients enrolled before and after 2010, respectively. The frequencies of chronic cluster headache (M:1.2%, F:1.4%) and aura (M:0.3%, F:0.7%) were low but similar between the sexes. Most headache features showed no difference between men and women. Female patients had significantly longer attack duration, shorter inter-bout duration, higher frequencies for eyelid edema, nausea and vomiting and lower frequencies for conjunctival injection and pacing. Sex difference did not influence headache-associated disability, anxiety, or depression, but poor sleep quality was significantly more common in women. Among menstruating women, 22/122 (18.0%) reported worsening headaches during menses. The effectiveness of treatment was similar between the sexes. CONCLUSIONS: Despite a decline of male-to-female ratio in the past two decades, most clinical profiles were similar between the sexes.

Non-aura visual disturbance with high visual aura rating scale scores has stronger association with migraine chronification than typical aura.

OBJECTIVES: To investigate the clinical correlates of visual symptoms in patients with migraine. METHOD: Patients with migraine that attended our headache clinics were enrolled. Headache profiles, disability, and comorbidities were acquired with structured questionnaires. A semi-structured visual phenomenon questionnaire was also used to assess the characteristics of visual symptoms, including visual aura in patients with migraine with aura and transient visual disturbance in patients with migraine without aura. Headache specialists interviewed with the participants for the ascertainment of diagnosis and verification of the questionnaires. RESULT: Migraine with aura patients with visual aura (n = 743, female/male = 2.3, mean age: 34.7 ± 12.2 years) and migraine without aura patients with non-aura transient visual disturbance (n = 1,808, female/male = 4.4, mean age: 39.4 ± 12.6 years) were enrolled. Patients with transient visual disturbance had higher headache-related disability and more psychiatric comorbidities. Chronic migraine was more common in migraine without aura than migraine with aura patients (41.9% vs. 11.8%, OR = 5.48 [95% CI: 4.33-7.02], p < 0.001). The associations remained after adjusting confounding factors. CONCLUSION: Presence of non-aura transient visual disturbance may suggest a higher migraine-related disability and is linked to higher risk of chronic migraine than typical migraine aura in migraine patients. Further studies are needed to elucidate the potential mechanism.

Most bothersome symptoms in patients with migraine: A hospital-based study in Taiwan.

OBJECTIVE: To investigate the distribution, clinical associations, and treatment responses for the most bothersome symptoms of migraine in a large sample of patients with migraine in Taiwan. BACKGROUND: The most bothersome symptom is recently recommended as a co-primary endpoint in clinical trials of acute treatment of migraine. However, most clinical trials and observational studies have been conducted in the United States and Europe, with photophobia representing the most common most bothersome symptom. METHODS: Patients who were newly diagnosed with migraine by headache specialists in Taipei Veterans General Hospital were recruited. All participants completed a questionnaire for headache profile, including the most bothersome symptom. Clinical associations of the most bothersome symptoms and response rates to previous acute treatments were analyzed. RESULTS: Among the recruited 1188 patients with migraine (female 79.4%, mean age 39.0 ± 12.1 years) in this cross-sectional study, nausea (n = 729/1188, 61.4%) was the most common symptom that was most bothersome, followed by phonophobia (n = 280/1188, 23.6%), and photophobia (n = 122/1188, 10.3%). The frequency ranking was the same regardless of sex and age. Compared to migraine without aura, migraine with aura was associated with photophobia (adjusted odds ratio [OR] = 2.97, 95% confidence interval [CI] 1.76-5.0, p < 0.001). Chronic migraine was associated with phonophobia (adjusted OR = 1.51, 95% CI 1.13-2.01, p = 0.005), but there was a lower chance for nausea (adjusted OR = 0.68, 95% CI 0.53-0.88, p = 0.004), as the most bothersome symptom. Patients with different most-bothersome symptoms responded similarly to previous acute treatments, with an overall response rate of 52.2% (n = 550/1053). CONCLUSION: Patients with migraine in Taiwan reported a distinct ranking of the most bothersome symptom. However, the response rates of the most bothersome symptom and headache were similar, which supports the most bothersome symptom as an outcome measure for acute treatment of migraine. Further studies recruiting different populations are required to investigate regional differences in most bothersome symptoms.

Resting State Electrophysiological Cortical Activity: A Brain Signature Candidate for Patients with Migraine.

PURPOSE OF REVIEW: Studies on event-related evoked potentials have indicated that altered cortical processing of sensory stimuli is associated with migraine. However, the results depend on the experimental method and patients. Electrophysiology of resting state cortical activity has revealed compelling results regarding the pathophysiology of migraine. This review summarized the available information related to patients with episodic and chronic migraine to determine whether certain features can be used as signatures for migraine. RECENT FINDINGS: A recent study examined differences in resting state functional connectivity among the pain-related regions and revealed that beta connectivity was attenuated in migraine and that altered connectivity in the anterior cingulate cortex was linked to migraine chronification. These findings suggested that chronification leads to neuroplasticity in the pain areas of higher-level processing rather than in areas involved in basic sensory discrimination (i.e., primary and secondary somatosensory areas). Another study discovered that the betweenness centrality of delta band in right precuneus was significantly lower in those with longer history of migraine. Electroencephalogram may also predict the treatment outcomes in patients with chronic migraine that those with lower pre-treatment occipital alpha power tend to show greater reduction in headache frequency. Studies on resting state activity have yielded convincing findings regarding aberrant oscillatory power and functional connectivity in relation to migraine, thus contributing to identifying brain signatures for migraine. The role of such assessment in precision medicine should be further investigated.

Dynamic brainstem and somatosensory cortical excitability during migraine cycles.

BACKGROUND: Migraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine. METHODS: Both patients underwent EEG recording of event-related potentials with the somatosensory and paired-pulse paradigms for 30 consecutive days. The migraine cycle was divided into the following phases: 24-48 h before headache onset (Pre2), within 24 h before headache onset (Pre1), during the migraine attack (Ictal), within 24 h after headache offset (Post1), and the interval of ˃48 h between the last and next headache phase (Interictal). The normalised current intensity in the brainstem and S1 and gating ratio in the S1 were recorded and examined. RESULTS: Six migraine cycles (three for each patient) were analysed. In both patients, the somatosensory excitability in the brainstem (peaking at 12-14 ms after stimulation) and S1 (peaking at 18-19 ms after stimulation) peaked in the Pre1 phase. The S1 inhibitory capability was higher in the Ictal phase than in the Pre1 phase. CONCLUSION: This study demonstrates that migraine is a cyclic excitatory disorder and that the neural substrates involved include the somatosensory system, starting in the brainstem and spanning subsequently to the S1 before the migraine occurs. Further investigations with larger sample sizes are warranted.

Resting-state magnetoencephalographic oscillatory connectivity to identify patients with chronic migraine using machine learning.

To identify and validate the neural signatures of resting-state oscillatory connectivity for chronic migraine (CM), we used machine learning techniques to classify patients with CM from healthy controls (HC) and patients with other pain disorders. The cross-sectional study obtained resting-state magnetoencephalographic data from 240 participants (70 HC, 100 CM, 35 episodic migraine [EM], and 35 fibromyalgia [FM]). Source-based oscillatory connectivity of relevant cortical regions was calculated to determine intrinsic connectivity at 1-40 Hz. A classification model that employed a support vector machine was developed using the magnetoencephalographic data to assess the reliability and generalizability of CM identification. In the findings, the discriminative features that differentiate CM from HC were principally observed from the functional interactions between salience, sensorimotor, and part of the default mode networks. The classification model with these features exhibited excellent performance in distinguishing patients with CM from HC (accuracy ≥ 86.8%, area under the curve (AUC) ≥ 0.9) and from those with EM (accuracy: 94.5%, AUC: 0.96). The model also achieved high performance (accuracy: 89.1%, AUC: 0.91) in classifying CM from other pain disorders (FM in this study). These resting-state magnetoencephalographic electrophysiological features yield oscillatory connectivity to identify patients with CM from those with a different type of migraine and pain disorder, with adequate reliability and generalizability.

Determinants of post-mydriatic intraocular pressure in phakic eyes with prevalent angle closure diseases.

PURPOSE: This study aimed to identify acute angle closure (AAC) risk following pharmacologic mydriasis and the factors affecting post-mydriatic intraocular pressure (IOP) in a population with a high prevalence of angle closure disease. METHODS: In total, 460 individuals aged ≥ 72 years were enrolled in this cross-sectional community-based screening program. IOP was measured at baseline and 1 hour after mydriasis. Individuals with post-mydriatic IOP spike > 6 mmHg received indentation gonioscopy and IOP-lowering medication. Linear regression analysis was used to identify ocular parameters associated with post-mydriatic IOP elevation. RESULTS: The mean age of participants was 77.8 ± 4.1 years, and 65.4% of them were men. In total, 21 eyes of 16 participants (3.48%) had post-mydriatic IOP spikes (range: 6-13.7 mmHg); among them, 15 eyes had an IOP of > 21 mmHg. None of the participants developed AAC. All eyes with IOP spikes were phakic, except for one with pseudophakic angle closure. Analysis of 381 participants with at least one phakic eye revealed that higher post-mydriatic IOP and IOP changes were associated with narrower angle grading, more extensive peripheral anterior synechiae, shallower central anterior chamber, and thicker lens. According to multiple linear regression analysis, post-mydriatic IOP was independently associated with baseline IOP and factors suggestive of crowded anterior chamber based on gonioscopic findings and central or peripheral anterior chamber depth evaluation in conjunction with lens thickness. CONCLUSION: Post-mydriatic IOP should be measured in phakic eyes with a crowded anterior chamber. Post-mydriatic IOP spikes can be effectively blunted with intervention to prevent AAC.

Brain Excitability in Tension-Type Headache: a Separate Entity from Migraine?

PURPOSE OF REVIEW: Tension-type headache is often regarded as the "normal" headache due to its high prevalence and mild disability in contrast with migraine. Clinically, both headaches are common comorbidities to each other. To date there has been many studies linked migraine to a brain excitability disorder. This review summarized earlier studies on brain excitability of TTH and discuss if TTH is a separate clinical entity from migraine as suggested by the diagnostic criteria. RECENT FINDINGS: A recent magnetoencephalographic study from our group enrolled patients with "strict-criteria" TTH (i.e., absence of any migraine characteristics and associated symptoms) to compare the somatosensory excitability with patients with migraine and controls. This study provided evidence that TTH and migraine differ in excitability profiles and the measurement of preactivation excitability was able to discriminate TTH from migraine. Earlier studies on brain excitability of TTH yielded negative findings or a common change shared with migraine. Future studies using strict diagnostic criteria to avoid the unwanted interference from migraine comorbidity may help decipher the "true" pathophysiology of TTH, which may pave the way to a TTH-specific brain signature and treatment.