The evolutionary meaning of migraine

Introduction: Migraine’s astonishing prevalence and preserved genetic background contrast with the definition of a disease and the biological meaning of experiencing recurrent, severe headache attacks is still puzzling. Methods: To provide a comprehensive explanation of the migraine evolutionary meaning, we review (i) the putative role of the autonomic nervous system in migraine attacks, (ii) the inter-ictal autonomic, functional, and metabolic signature of migraine patients, (iii) the bio-behavioral perspective of pain, and (iv) the allostatic perception of migraine chronification. Results: Migraineurs have inter-ictal cortical hyperexcitability and metabolic dysfunction that predisposes to brain energetic imbalance. Multiple precipitating factors may lead to brain energy consumption over the migraine attack generation threshold. In response, the brain engenders adaptive, evolutionary conserved, autonomic-behavior responses through the antidromic activation of the trigeminovascular system. The sickness behavior and severe pain experienced during migraine attacks result in avoiding mental and physical activity, allowing brain energy restoration. Chronic exposure to stressors may result in an allostatic overload, leading to maladaptive chronic activation of these responses. In this bio-behavioral perspective, the chronification of migraine should be envisioned as a pathological process, whereas the migraine itself should not. Conclusion: Migraine has an evolutionary (Darwinian) meaning

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

Precision viticulture: Automatic selection of the regions of interest from moving wagon hyperspectral images of grapes for efficient SSC prediction

Precision viticulture is increasingly being applied to automate and optimize grape production in the vineyard. This paper describes the development of a method for automatic selection of regions of interest from hyper- spectral images obtained of a row of vines and intended for prediction of soluble solids content. For this purpose, a dataset consisting of hyperspectral images of a row of ‘Sangiovese ’ wine grapes was adopted. Hyperspectral images were acquired directly in the field by means of a hyperspectral imaging Vis/NIR system (400 – 1000 nm) mounted on a ground-based vehicle. The analyses were carried out on 17 different days, under clear or partly cloudy conditions, in the period between post-veraison and harvest. The vineyard row of Sangiovese vines was divided into 11 sections and a hyperspectral image for each section for each day of analysis was acquired. The regions of interest of the hyperspectral images, comprising the areas representing the grapes, were selected using a PLS-DA-based method. The best PLS-DA model provided excellent results, with sensitivity and specificity values of 0.991 and 0.996, respectively. The mean spectra of the selected regions of interest (ROI) were finally used to predict the soluble solids content (SSC) of the grapes by PLS regression to a primary reference analysis. The results of SSC predictions using the automatic selection of ROIs (R2CV = 0.74 and RMSECV = 0.86 ◦ Brix) were on par with similar regression based on carefully manual selection of ROIs (R2CV = 0.73 and RMSECV = 0.87 ◦ Brix)

Modified atmosphere packaging of hen table eggs: Effects on functional properties of albumen

The aim of this study was to compare technological properties (gel hardness, foam drainage, and meringue crispness) of albumen of nonpacked table eggs (control) with those of eggs packed in high-barrier plastic pouches with 3 modified atmosphere packaging (MAP) conditions (air, 100% N2, and 100% CO2) during 28 d of storage at 25°C. The values of gel hardness for the control sample showed an increasing trend, demonstrating the highest values throughout the experiment duration compared with the other samples. This behavior was probably attributable to the pH increase detected only for this sample during storage (from 8.82 ± 0.06 for fresh egg to 9.96 ± 0.06 at the end of the experiment). Air and N2 samples showed constant and similar hardness values during storage. The hardness of coagulated albumen showed a strict correlation with raw albumen pH (r2 = 0.929; P < 0.001). Other than reducing albumen pH during storage, MAP with CO2 caused the formation of a soft and puffy coagulum with very low hardness, reaching the lowest value of 1.26 ± 0.38 N after 4 d of storage, that slowly increased to 2.11 ± 0.49 N at the end of the experiment. Foam stability decreased during storage for all samples, but CO2 eggs showed a significantly (P < 0.05) higher foam stability than fresh eggs until 15 d, reaching values similar to those of the other samples only at the end of the storage time. Packing eggs in CO2 promoted an improvement of meringue crispness. The application of this atmosphere could ameliorate the quality characteristics of albumen-based food products. Commercially, CO2 MAP could provide an albumen-based ingredient tailored to maximize the characteristics needed in the final product (e.g., fresh shell eggs special for meringue preparation) that could give an added value to the product

Prevalence, natural history and dynamic nature of chronic headache and medication overuse headache in Italy: The SPARTACUS study

Background: Chronic headaches and medication overuse headache are common and burdening conditions. No studies have evaluated the prevalence of chronic headache and medication overuse headache in an unselected Italian population. Methods: We performed a three-year cross-sectional and longitudinal population-based study to investigate prevalence, natural history, and prognostic factors of chronic headache. We delivered a self-administered questionnaire to 25,163 subjects. Chronic headache patients were interviewed by General Practitioners. After three years, medication overuse headache patients were invited to undergo a neurological evaluation at our Center. Results: 16,577 individuals completed the questionnaire; 6878 (41,5%) were episodic headache sufferers and 636 (3.8%) were chronic headache subjects. 239 (1.4%) patients were acute medication over-users. All medication overuse headache patients had migraine or headache with migrainous features. At the three-year follow-up of 98 patients, we observed conversion to episodic headaches in 53 (54.1%) patients. 27 (50.9%) patients remitted spontaneously. Conclusions: We present the first prevalence data on chronic headache and medication overuse headache in an unselected Italian population and a high rate of spontaneous remission. These data support the interpretation of medication overuse headache as a specific migraine-related disorder that may reflect chronic migraine’s dynamic nature, the need for more specific medication overuse headache diagnostic criteria, and highlight the priority of targeted public health policies

A real-world study on unmet medical needs in triptan-treated migraine: Prevalence, preventive therapies and triptan use modification from a large Italian population along two years

Although migraine is a disabling neurological condition that causes important disability, it remains an area of underdiagnosis and undertreatment worldwide. The aim of this study was to depict the burden of the unmet medical needs in migraine treated with triptans in a large Italian population

Great occipital nerve long-acting steroid injections in cluster headache therapy: an observational prospective study

Background: Injections targeting the occipital nerve are used to reduce headache attacks and abort cluster bouts in cluster headache patients. There is no widely accepted agreement over the optimal technique of injection, type and doses of steroids and/or anesthetics to use, as well as injection regimens. The aim of this study was to verify the effectiveness and safety of greater occipital nerve long-acting steroid injections in the management of episodic and chronic cluster headache. Methods: We conducted a prospective observational cohort study on episodic (ECH) and chronic cluster headache patients (CCH). ECH were included in the study at the beginning of a cluster period. Three injections with 60&nbsp;mg methylprednisolone were performed on alternate days. We registered the frequency and intensity of attacks three days before and 3, 7 and 30&nbsp;days after the treatment, the latency of cluster relapse, adverse events, scores evaluating anxiety (Zung scale), depression (Beck’s Depression Scale) and quality of life (Disability Assessment Schedule II, 12-Item Self-Administered Version). Primary outcome was the interruption of the cluster after the three injections. Responders conducted a follow-up period of 12&nbsp;months. Results: We enrolled 60 patients, 47 with ECH and 13 with CCH. We observed a complete response in 47.8% (22/46) of episodic and 33.3% (4/12) of chronic patients. Moreover, a partial response (reduction of at least 50% of attacks) was obtained in further 10.8% (5/46) of episodic and in 33.3% (4/12) of chronic patients at 1&nbsp;month. Median pain-free period was of 3&nbsp;months for CCH responders. Only mild adverse events were reported in 38.3% (23/58) cases. Conclusions: We suggest three greater occipital nerve injections of 60&nbsp;mg methylprednisolone on alternate days as useful therapy in episodic and chronic cluster headache. This leads to a long pain-free period in chronic forms. Adverse effects are mild and support its use as first choice. Trial registration: The study was inserted in AIFA observational studies register

Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy

The authors used 1H-MRS to investigate hypothalamic metabolism in 26 patients with cluster headache (CH) and 12 healthy subjects. Hypothalamic N-acetylaspartate/creatine was reduced in patients with CH vs controls (p < 0.01). Dividing the patients into episodic CH outside- and in-cluster periods and chronic CH, the hypothalamic N-acetylaspartate/creatine in all three subgroups of patients was reduced. The reduction of the neuronal marker N-acetylaspartate is consistent with hypothalamic neuronal dysfunction in patients with CH

Migraine chronification as an allostatic disorder: a proof-of-concept study

Objective: The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification. Methods: This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group). Results: The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07–7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p &lt; 0.001), and heart rate (p = 0.019). Conclusion: Our study substantiates this emerging concept of migraine chronification as an allostatic disorder

The effects of cerebrospinal fluid tap-test on idiopathic normal pressure hydrocephalus: an inertial sensors based assessment

BACKGROUND: Gait disturbances are typical of persons with idiopathic normal pressure hydrocephalus (iNPH) without signs distinctive from other neurodegenerative and vascular conditions. Cerebrospinal fluid tap-test (CSF-TT) is expected to improve the motor performance of iNPH patients and is a prognostic indicator in their surgical management. This observational prospective study aims to determine which spatio-temporal gait parameter(s), measured during instrumented motor tests, and clinical scale(s) may provide a relevant contribution in the evaluation of motor performance pre vs. post CSF-TT on iNPH patients with and without important vascular encephalopathy. METHODS: Seventy-six patients (20 with an associated vascular encephalopathy) were assessed before, and 24 and 72\u2009h after the CSF-TT by a timed up and go test (TUG) and an 18\u2009m walking test (18\u2009mW) instrumented using inertial sensors. Tinetti Gait, Tinetti Balance, Gait Status Scale, and Grading Scale were fulfilled before and 72\u2009h after the CSF-TT. Stride length, cadence and total time were selected as the outcome measures. Statistical models with mixed effects were implemented to determine the relevant contribution to response variables of each quantitative gait parameter and clinical scales. RESULTS AND CONCLUSION: From baseline to 72\u2009h post CSF-TT patients improved significantly by increasing cadence in 18\u2009mW and TUG (on average of 1.7 and 2.4 strides/min respectively) and stride length in 18\u2009mW (on average of 3.1\u2009cm). A significant reduction of gait apraxia was reflected by modifications in double support duration and in coordination index. Tinetti Gait, Tinetti Balance and Gait Status Scale were able to explain part of the variability of response variables not covered by instrumental data, especially in TUG. Grading Scale revealed the highest affinity with TUG total time and cadence when considering clinical scales alone. Patients with iNPH and an associated vascular encephalopathy showed worst performances compared to pure iNPH but without statistical significance. Gait improvement following CSF-TT was comparable in the two groups. Overall these results suggest that, in order to augment CSF-TT accuracy, is key to assess the gait pattern by analyzing the main spatio-temporal parameters and set post evaluation at 72\u2009h. TRIAL REGISTRATION: Approved by ethics committee: CE 14131 23/02/2015