Diagnostic biomarker discovery from brain EEG data using LSTM, reservoir-SNN, and NeuCube methods in a pilot study comparing epilepsy and migraine.

The study introduces a new online spike encoding algorithm for spiking neural networks (SNN) and suggests new methods for learning and identifying diagnostic biomarkers using three prominent deep learning neural network models: deep BiLSTM, reservoir SNN, and NeuCube. EEG data from datasets related to epilepsy, migraine, and healthy subjects are employed. Results reveal that BiLSTM hidden neurons capture biological significance, while reservoir SNN activities and NeuCube spiking dynamics identify EEG channels as diagnostic biomarkers. BiLSTM and reservoir SNN achieve 90 and 85% classification accuracy, while NeuCube achieves 97%, all methods pinpointing potential biomarkers like T6, F7, C4, and F8. The research bears implications for refining online EEG classification, analysis, and early brain state diagnosis, enhancing AI models with interpretability and discovery. The proposed techniques hold promise for streamlined brain-computer interfaces and clinical applications, representing a significant advancement in pattern discovery across the three most popular neural network methods for addressing a crucial problem. Further research is planned to study how early can these diagnostic biomarkers predict an onset of brain states.

Assessing the impact of migraine on benign paroxysmal positional vertigo symptoms and recovery.

BACKGROUND: During episodes of benign paroxysmal positional vertigo (BPPV), individuals with migraine, compared with individuals without migraine, may experience more severe vestibular symptoms because of their hyperexcitable brain structures, more adverse effects on quality of life, and worse recovery processes from BPPV. METHODS: All patients with BPPV were assigned to the migraine group (MG, n = 64) and without migraine group (BPPV w/o MG, n = 64) and completed the Vertigo Symptom Scale (VSS), Vertigo Dizziness Imbalance Symptom Scale (VDI-SS), VDI Health-Related Quality of Life Scale (VDI-HRQoLS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) at the time of BPPV diagnosis (baseline) and on the one-month follow-up. Headache Impact Test-6 and Migraine Disability Assessment Scale were used for an assessment of headache. Motion sickness was evaluated based on the statement of each patient as present or absent. RESULTS: Compared with the BPPV w/o MG, the MG had higher VSS scores at baseline [19.5 (10.7) vs. 11.3 (8.5); p < 0.001] and on one-month follow-up [10.9 (9.3) vs. 2.2 (2.7), p < 0.001]; experienced more severe dizziness and imbalance symptoms based on the VDI-SS at baseline (61.9% vs. 77.3%; p < 0.001) and after one month (78.9% vs. 93.7%, p < 0.001); and more significantly impaired quality of life according to the VDI-HRQoLS at baseline (77.4% vs. 91.8%, p < 0.001) and after one month (86.3% vs. 97.6%, p < 0.001). On the one-month follow-up, the subgroups of patients with moderate and severe scores of the BAI were higher in the MG (39.2%, n = 24) than in the BPPV w/o MG (21.8%, n = 14) and the number of patients who had normal scores of the BDI was lower in the MG than in the BPPV w/o MG (67.1% vs. 87.5%, p = 0.038). CONCLUSION: Clinicians are advised to inquire about migraine when evaluating patients with BPPV because it may lead to more intricate and severe clinical presentation. Further studies will be elaborated the genuine nature of the causal relationship between migraine and BPPV.

Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail.

BACKGROUND: Migraine is a leading cause of disability worldwide. Several retrospective studies have suggested that the closure of the Patent Foramen Ovale (PFO) may provide relief from migraines. However, three randomized controlled trials did not meet their primary endpoints regarding migraine cessation, reduction in monthly migraine days, and responder rates. METHODS: The SPRING study is a multicenter, prospective, randomized, and open-label trial designed to compare the effectiveness and safety of PFO closure versus medication in the relief of migraines. The primary endpoint is the total cessation of migraines, as recorded in patient headache diaries during the follow-up period. Additional diagnostic tools include echocardiography with agitated saline contrast, transcranial Doppler, and routine laboratory measurements. CONCLUSION: The SPRING trial aims to assess the effectiveness and safety of PFO closure versus medication in mitigating migraines in real-world settings. (Clinical Trails ID: NCT04946734).

Identification and characterization of migraine in pregnancy: A Norwegian registry-based cohort study.

BACKGROUND: Migraine is common in women of reproductive age. Migraine's episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. METHODS: We linked four registries to detect pregnancies from 2009-2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. RESULTS: We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%-4.3% before, and 0.8%-1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. CONCLUSIONS: Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.

[A comparative assessment of microbiocenosis of saliva and oropharynx in patients with migraine]. / Sravnitel'naya otsenka mikrobiotsenoza slyuny i rotoglotki u patsientov s migren'yu.

OBJECTIVE: To identify changes in the microbiome of saliva and to compare it with the microbiome of the oropharynx of patients with migraine. MATERIAL AND METHODS: Sixty patients with migraine (21-56 years old), were examined using a headache diary, MIDAS and VAS. A microbiological examination of saliva and smear from the mucosa of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with the determination of 57 microorganisms was performed. All patients had comorbid chronic diseases of the gastrointestinal tract and upper respiratory tract (URT), according to anamnestic data and examination by specialists. RESULTS: A significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of URT (strepto- and staphylococci); markers of transient microorganisms characteristic of intestinal microflora (clostridia, gram-negative rods, anaerobes) that are normally absent; viral markers of cytomegaloviruses and herpes groups; a decrease in the content of fungi were identified in saliva. A comparative analysis of the microbiome of saliva and oropharynx showed: 1) a significant decrease in the concentration of coccal flora Enterococcus spp., Streptococcus mutans, Staphylococcus aureus, anaerobic bacteria Clostridium difficile and Clostridium perfringens in saliva; enterobacteria Helicobacter pylori; gram-negative rods Kingella spp., fungi and Epstein-Barr virus; 2) an increase in salivary concentrations of Staphylococcus epidermidis, anaerobic Clostridium ramosum and Fusobacterium spp./Haemophilus spp. and gram-negative bacilli Porphyromonas spp. CONCLUSION: A comparative assessment of the microbiota of a smear from the posterior wall of the oropharynx and saliva using MMSM showed the presence of dysbiosis both in the oropharynx and in the saliva of patients with migraine. However, there were fewer deviations from the norm in saliva, therefore, for diagnostic purposes, a smear from the posterior wall of the oropharynx is more significant as a biomarker for patients with migraine.

Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

BACKGROUND: Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. METHODS: Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. RESULTS: Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. CONCLUSIONS: A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT04574362 Date registered: 2020-10-05.

Posttraumatic Headache.

OBJECTIVE: This article provides an overview of the epidemiology, diagnosis, clinical presentation, pathophysiology, prognosis, and treatment of posttraumatic headache attributed to mild traumatic brain injury (mTBI). LATEST DEVELOPMENTS: The International Classification of Headache Disorders, Third Edition requires that posttraumatic headache begin within 7 days of the inciting trauma. Although posttraumatic headache characteristics and associated symptoms vary, most commonly there is substantial overlap with symptoms of migraine or tension-type headache. New insights into posttraumatic headache pathophysiology suggest roles for neuroinflammation, altered pain processing and modulation, and changes in brain structure and function. Although the majority of posttraumatic headache resolves during the acute phase, about one-third of individuals have posttraumatic headache that persists for at least several months. Additional work is needed to identify predictors and early markers of posttraumatic headache persistence, but several potential predictors have been identified such as having migraine prior to the mTBI, the total number of TBIs ever experienced, and the severity of initial symptoms following the mTBI. Few data are available regarding posttraumatic headache treatment; studies investigating different treatments and the optimal timing for initiating posttraumatic headache treatment are needed. ESSENTIAL POINTS: Posttraumatic headache begins within 7 days of the causative injury. The characteristics of posttraumatic headache most commonly resemble those of migraine or tension-type headache. Posttraumatic headache persists for 3 months or longer in about one-third of individuals. Additional studies investigating posttraumatic headache treatment are needed.

The right amygdala and migraine: Analyzing volume reduction and its relationship with symptom severity.

This study aimed to explore the relationship between gray matter volume changes and various clinical parameters in patients with migraine, focusing on symptom severity, quality of life, and states of depression and anxiety. Using a case-control design, we examined 33 patients with migraine, with or without aura, and 27 age-matched healthy subjects. We used magnetic resonance imaging to assess the volumes of 140 bilateral brain regions. Clinical evaluations included the Migraine Disability Assessment, the Migraine Specific Quality of Life Questionnaire, the Center for Epidemiologic Studies Depression scale, Spielberger's State and Trait Anxiety scales, and the Japanese version of the Montreal Cognitive Assessment. We compared the scores of these measures between migraine patients and healthy controls to examine the interplay between brain structure and clinical symptoms. Significant volumetric differences were observed in the pallidum and amygdala between migraine patients and healthy individuals. The reduction in the right amygdala volume correlated significantly with migraine severity as measured by the Migraine Disability Assessment. Path analysis revealed a model where Migraine Disability Assessment scores were influenced by Migraine Specific Quality of Life Questionnaire outcomes, which were further affected by depression, anxiety, and a low right pallidum volume. Our findings suggest that the chronicity and severity of migraine headaches specifically affect the right amygdala. Our path model suggests a complex relationship whereby migraine disability is strongly influenced by quality of life, which is, in turn, affected by psychological states, such as anxiety and depression.

Migraine treatment: quo vadis? Real-world data study (2015-2022) in Spain.

BACKGROUND: Migraine is a leading cause of disability, estimated to affect one-in-ten people in Spain. This study aimed to describe the management of migraine in Spain and identify improvement areas. METHODS: Non-interventional, retrospective, cross-sectional cohort study conducted using an electronic medical records database covering visits to public healthcare providers for 3% of the Spanish population. Patients with a migraine diagnosis (ICD-9 346) between 01/2015 and 04/2022 were included, as well as their demographic and clinical characteristics, prescribed migraine treatments and the specialty of the prescribing physicians. RESULTS: The database included 61,204 patients diagnosed with migraine. A migraine treatment had been prescribed to 50.6% of patients over the last 24 months (only acute to 69.5%, both acute and preventive to 24.2%, and only preventive to 6.3%). The most frequently prescribed treatments were NSAIDs (56.3%), triptans (44.1%) and analgesics (28.9%). Antidepressants were the most common preventive treatment (prescribed to 17.9% of all treated patients and 58.7% of those treated with a preventive medication), and anti-CGRP monoclonal antibodies the least prescribed (1.7%; 5.7%). In 13.4% of cases, preventive medications were the first treatment: alone in 5.8% of cases and together with an acute medication in 7.6%. A fifth of patients who were initially prescribed with only acute treatment were later prescribed a preventive medication (20.7%). On average, it took 29.4 months for this change to occur. Two-thirds of patients started their preventive treatment in primary care (64.2%). The percentage of patients treated by a neurologist increased with the number of received preventive medications. However, 28.8% of patients who had already been prescribed five or more distinct preventive treatments were not treated by a neurologist. Migraine patients had between 1.2- and 2.2-times higher prevalence of comorbidities than the general population, age-gender adjusted. CONCLUSIONS: Our study emphasizes the need for improved management of migraine in Spain to reduce the risk of chronification and improve patient outcomes. More training and coordination across healthcare professionals is necessary to recognize and address risk factors for migraine progression, including multiple associated comorbidities and several lines of treatment, and to provide personalized treatment plans that address the complex nature of the condition.

Prospective diagnostic accuracy study of history taking and physical examination for adults with vertigo in general practice: study protocol.

INTRODUCTION: Vertigo is a prevalent and burdensome symptom. More than 80% of patients with vertigo are primarily treated by their general practitioner (GP) and are never referred to a medical specialist. Despite this therapeutic responsibility, the GP's diagnostic toolkit has serious limitations. All recommended tests lack empirical evidence, because a diagnostic accuracy study on vestibular disorders ('How well does test x discriminate between patients with or without target condition y?') has never been performed in general practice. The VERtigo DIagnosis study aims to fill this gap. METHODS AND ANALYSIS: We will perform a diagnostic accuracy study on vertigo of primary vestibular origin in general practice to assess the discriminative ability of history taking and physical examination. We will compare all index tests with a respective reference standard. We will focus on five target conditions that account for more than 95% of vertigo diagnoses in general practice: (1) benign paroxysmal positional vertigo, (2) vestibular neuritis, (3) Ménière's disease, (4) vestibular migraine (VM) and (5) central causes other than VM. As these five target conditions have a different pathophysiology and lack one generally accepted gold standard, we will use consensus diagnosis as a construct reference standard. Data for each patient, including history, physical examination and additional tests as recommended by experts in an international Delphi procedure, will be recorded on a standardised form and independently reviewed by a neurologist and otorhinolaryngologist. For each patient, the reviewers have to decide about the presence/absence of each target condition. We will calculate sensitivity, specificity, predictive values, likelihood ratios and diagnostic ORs, followed by decision rules for each target condition. ETHICS AND DISSEMINATION: The study obtained approval from the Vrije Universiteit Medical Center Medical Ethical Review Committee (reference: 2022.0817-NL83111.029.22). We will publish our findings in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ISRCTN97250704.

Increased CX3CL1 in cerebrospinal fluid and ictal serum t-tau elevations in migraine: results from a cross-sectional exploratory case-control study.

BACKGROUND: To date, migraine is diagnosed exclusively based on clinical criteria, but fluid biomarkers are desirable to gain insight into pathophysiological processes and inform clinical management. We investigated the state-dependent profile of fluid biomarkers for neuroaxonal damage and microglial activation as two potentially relevant aspects in human migraine pathophysiology. METHODS: This exploratory study included serum and cerebrospinal fluid (CSF) samples of patients with migraine during the headache phase (ictally) (n = 23), between attacks (interictally) (n = 16), and age/sex-matched controls (n = 19). Total Tau (t-Tau) protein, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured with the Neurology 4-plex kit on a Single Molecule Array SR-X Analyzer (Simoa® SR-X, Quanterix Corp., Lexington, MA). Markers of microglial activation, C-X3-C motif chemokine ligand 1 (CX3CL1) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), were assessed using an immunoassay. RESULTS: Concentrations of CX3CL1 but not sTREM2 were significantly increased both ictally and interictally in CSF but not in serum in comparison to the control cohort (p = 0.039). ROC curve analysis provided an AUC of 0.699 (95% CI 0.563 to 0.813, p = 0.007). T-Tau in serum but not in CSF was significantly increased in samples from patients taken during the headache phase, but not interictally (effect size: η2 = 0.121, p = 0.038). ROC analysis of t-Tau protein in serum between ictal and interictal collected samples provided an AUC of 0.729 (95% CI 0.558 to 0.861, p = 0.006). The other determined biomarkers for axonal damage were not significantly different between the cohorts in either serum or CSF. DISCUSSION: CX3CL1 in CSF is a novel potential fluid biomarker of migraine that is unrelated to the headache status. Serum t-Tau is linked to the headache phase but not interictal migraine. These data need to be confirmed in a larger hypothesis-driven prospective study.

Reconceptualizing autonomic function testing in migraine: a systematic review and meta-analysis.

BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

Migraine headache and other risk factors associated with glaucoma among the adult population living in Armenia: a case-control study.

PURPOSE: This study aimed to assess the association between migraine headache and glaucoma among the adult population living in Armenia. METHODS: This case-control study recruited 145 cases with glaucoma and 250 controls without glaucoma and other ocular disorders except refractive error from Optomed Canada Diagnostic Eye Center in Armenia. A structured questionnaire contained questions on socio-demographics, family history of glaucoma and stroke, ocular health, smoking, migraine, and obstructive sleep apnea. The Migraine Screening Questionnaire assessed possible migraine and the Berlin Questionnaire measured obstructive sleep apnea. RESULTS: The mean ages of cases and controls were 63.3 (SD = 12.3) and 39.5 (SD = 13.5), respectively. Females comprised 62.8% of cases and 69.1% of controls. A total of 17.8% of cases and 19.0% of controls had possible migraine. In the adjusted analysis older age (OR 1.17; 95% CI 1.12; 1.23), average/lower than average socio-economic status (OR 5.27; 95% CI 1.30; 21.3), and family history of glaucoma (OR 4.25; 95% CI 1.51; 11.9) were associated with high-tension glaucoma. CONCLUSION: Timely case detection of glaucoma among those with average/low socio-economic status and those with family history of glaucoma could prevent further progression of the disease. Further studies to explore the relationship between migraine headache and specific types of glaucoma may be worthwhile.

Acute Treatment of Migraine.

OBJECTIVE: Most patients with migraine require acute treatment for at least some attacks. This article reviews the approach to the acute treatment of migraine, migraine-specific and nonspecific treatment options, rescue treatment and options for management in the emergency department and inpatient settings, and treatment during pregnancy and lactation. LATEST DEVELOPMENTS: Triptans, ergot derivatives, and nonsteroidal anti-inflammatory drugs have historically been the main acute treatments for migraine. The development of new classes of acute treatment, including the small-molecule calcitonin gene-related peptide receptor antagonists (gepants) and a 5-HT1F receptor agonist (lasmiditan), expands available options. These new treatments have not been associated with vasospasm or increased cardiovascular risk, therefore allowing migraine-specific acute treatment for the more than 20% of adults with migraine who are at increased risk of cardiovascular events. Neuromodulation offers a nonpharmacologic option for acute treatment, with the strongest evidence for remote electrical neuromodulation. ESSENTIAL POINTS: The number of available migraine treatments continues to expand, although triptans are still the mainstay of migraine-specific acute treatment. There is no one-size-fits-all acute treatment and multiple treatment trials are sometimes necessary to determine the optimal regimen for patients. Switching within and between classes, using the maximum allowed dose, using combination therapy, and counseling patients to treat early are all strategies that may improve patient response to acute treatment.

New Daily Persistent Headache.

OBJECTIVE: This article describes the clinical features, etiology, differential diagnosis, management, and prognosis of new daily persistent headache. LATEST DEVELOPMENTS: New daily persistent headache has attracted renewed attention as it may arise in the setting of a COVID-19 infection. Spontaneous intracranial hypotension, particularly from CSF-venous fistulas, remains an important secondary headache disorder to consider before diagnosing new daily persistent headache. Symptomatic treatment for new daily persistent headache may include acute and preventive therapies used for migraine and tension-type headache, such as triptans, oral preventive agents, onabotulinumtoxinA, and agents that target calcitonin gene-related peptide. ESSENTIAL POINTS: New daily persistent headache is a daily headache syndrome that starts acutely and can only be diagnosed after 3 months have elapsed and other secondary and primary headache diagnoses have been excluded. The clinical manifestations largely resemble either chronic migraine or chronic tension-type headache. The underlying cause is unknown, but it is plausible that multiple etiologies exist and that it is not a single disease entity. The prognosis is variable but often poor, and the treatment approach is largely extrapolated from the management of chronic migraine and chronic tension-type headache.

Vestibular migraine: an update.

PURPOSE OF REVIEW: We performed a narrative review of the recent findings in epidemiology, clinical presentation, mechanisms and treatment of vestibular migraine. RECENT FINDINGS: Vestibular migraine is an underdiagnosed condition that has a high prevalence among general, headache and neuro-otology clinics. Vestibular migraine has a bimodal presentation probably associated with a hormonal component in women. These patients could have a complex clinical phenotype including concomitant autonomic, inflammatory or connective tissue conditions that have a higher prevalence of psychological symptoms, which may mistakenly lead to a diagnosis of a functional neurological disorder. A high proportion of patients with postural perceptual persistent dizziness have a migraine phenotype. Independently of the clinical presentation and past medical history, patients with the vestibular migraine phenotype can respond to regular migraine preventive treatments, including those targeting the calcitonin gene-related peptide pathways. SUMMARY: Vestibular migraine is an underdiagnosed migraine phenotype that shares the pathophysiological mechanisms of migraine, with growing interest in recent years. A thorough anamnesis is essential to increase sensitivity in patients with unknown cause of dizziness and migraine treatment should be considered (see supplemental video-abstract).

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. METHODS: Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. RESULTS: Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2-54.4) and 4.6 (2.4-6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. CONCLUSIONS: We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations.

Neurocysticercosis Presenting as Migraine in the United States.

BACKGROUND Cysticercosis is a condition caused by infection with the larval form of Taenia solium, a pork tapeworm that uses pigs as an intermediate host. Humans become infected when they ingest water or food contaminated with tapeworm cysts. Cysticercosis is increasing in frequency in developed countries due to increased access to travel. Neurocysticercosis occurs when Taenia solium cysts embed within the nervous system. The clinical presentation of neurocysticercosis ranges from asymptomatic to life-threatening, largely depending on the brain parenchymal involvement. The diagnosis is typically made with a combination of clinical evaluation, serology, and neuroimaging. Treatment for parenchymal neurocysticercosis may involve anthelmintic agents, symptomatic agents, surgery, or a combination of methods. CASE REPORT A 52-year-old man with a medical history of migraine headaches, complicated type 2 diabetes mellitus, and obesity presented with a 4-month change in his migraines becoming severe, worse over his occiput bilaterally, and unresponsive to abortive therapy. His exposure history was unremarkable except for a habit of eating undercooked bacon, by which he would have developed neurocysticercosis via autoinfection. Neuroimaging and serology confirmed a diagnosis of neurocysticercosis and he was treated accordingly with antiparasitic and anti-inflammatory medications. CONCLUSIONS This presentation is nonspecific and can easily be overlooked, especially if there is an underlying known neurological condition such as migraine. This case illustrates that neurocysticercosis should be considered when an existing neuropathological condition displays a change in presentation or requires a change in therapeutic management, even without obvious risk factors.

Shared comorbidity of depression, migraine, insomnia, and fibromyalgia in a population-based sample.

BACKGROUND: Depression, migraine, insomnia, and fibromyalgia are reportedly comorbidities. Nevertheless, no study has evaluated the comorbidity of all four of these disorders. This study aimed to investigate the comorbidity of these four disorders. METHODS: Cross-sectional analyses were performed using data of the Circannual Change in Headache and Sleep study, an online nationwide population-based survey. Validated questionnaires were used to diagnose the disorders and measure quality of life. The change of clinical characteristics by addition of any comorbidity was analyzed using the Jonckheere-Terpstra trend test. RESULTS: The prevalence rates of depression, migraine, insomnia, and fibromyalgia were 7.2 %, 5.6 %, 13.3 %, and 5.8 %, respectively. Among the 3030 included participants, 494 (16.3 %), 164 (5.4 %), 40 (1.3 %), and 6 (0.2 %) had one, two, three, and four of these conditions, respectively. The number of headache days per 30 days (Jonckheere-Terpstra trend test, p = 0.011) and migraine-related disability (migraine disability assessment score, p = 0.021) increased with an increase in the number of comorbidities but not with the intensity of headache (visual analog scale, p = 0.225) among participants with migraine. The severity of insomnia (Insomnia Severity Index, p < 0.001) and fibromyalgia (fibromyalgia severity score, p = 0.002) increased with additional comorbidities; however, depression (Patient Health Questionnaire-9, p = 0.384) did not show such an increase. LIMITATIONS: The diagnoses of conditions were based on self-reported questionnaires. CONCLUSIONS: The findings confirmed significant comorbidity between depression, migraine, insomnia, and fibromyalgia. Health professionals should be aware of the probable comorbidity of depression, migraine, insomnia, and fibromyalgia when caring for individuals with any of these four disorders.