Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation.

OBJECTIVE: Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. MATERIALS AND METHODS: The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. RESULTS: Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. CONCLUSION: We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH.

Mechanosensitive receptors in migraine: a systematic review.

BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

Leaky gut and inflammatory biomarkers in a medication overuse headache model in male rats.

Background/aim: Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are not completely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is to investigate the role of leaky gut and inflammation in an MOH model MOH model in male rats. Methods: The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronic NSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and the second group was the vehicle group (n = 8) that received 5% dimethyl sulfoxide+sesame oil (ip) for 4 weeks. We assessed spontaneous pain-like behavior, periorbital mechanical withdrawal thresholds, and anxiety-like behavior using an elevated plus maze test. After behavioral testing, serum levels of occludin and lipopolysaccharide-binding protein (LBP) and brain levels of IL-17, IL-6, and high mobility group box 1 protein (HMGB1) were evaluated with ELISA.Results: Serum LBP and occludin levels and brain IL-17 and HMGB1 levels were significantly elevated in the chronic NSAID group compared to its vehicle (p = 0.006, p = 0.016, p = 0.016 and p = 0.016 respectively) while brain IL-6 levels were comparable (p = 0.67) between the groups. The chronic NSAID group showed pain-like and anxiety-like behavior in behavioral tests. Brain IL-17 level was positively correlated with number of head shakes (r = 0.64, p = 0.045), brain IL-6 level was negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.71, p = 0.049), and serum occludin level was positively correlated with grooming duration (r = 0.73, p = 0.032) in chronic NSAID group. Conclusion: Elevated serum occludin and LBP levels and brain IL-17 and HMGB1 levels indicate a possible role of leaky gut and inflammation in an MOH model in male rats. Additionally, a significant correlation between pain behavior and markers of inflammation and intestinal hyperpermeability, supports the role of inflammation and leaky gut in MOH pathophysiology.

Placebo and nocebo in the treatment of migraine: How much does real world effectiveness depend on contextual effects?

PURPOSE: Treatments in medicine impact individuals beyond their intended effects, due to phenomena such as the placebo and nocebo effects. The placebo effect arises from the positive expectation of a treatment being beneficial, while the nocebo effect stems from the negative expectation of a treatment causing harm. Both in real-world practice and clinical trials, treatments can lead to outcomes unrelated to their intended mechanism of action, which we categorize as placebo and nocebo responses. These responses, combined with the inherent fluctuation in a condition's natural progression, regression to the mean, and random comorbidities, make up a significant part of the therapeutic experience. Particularly in pain management, placebo and nocebo effects play a substantial role. By addressing modifiable contextual factors such as patient expectations, lifestyle choices, and the therapeutic relationship, healthcare providers can enhance the effectiveness of migraine treatments, paving the way for a more comprehensive, individualized approach to patient care. We must also consider non-modifiable factors like personal experiences, beliefs, and information from social media and the internet. CONCLUSION: This review offers a summary of our current understanding of the placebo and nocebo effects in migraine management.

Visual temporal discrimination is impaired in patients with migraine without aura.

BACKGROUND AND OBJECTIVE: Dysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test. METHODS: A total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light-emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack. RESULTS: The VTDT of each visual field in both attack (mean [SD] 102.3 [38.4] ms for the right visual field and 106.3 [52.2] ms for the left) and the interictal periods (mean [SD] 75.2 [27.9] ms for the right and 78.2 [27.9] ms for the left) were significantly higher than in the control group (mean [SD] 45.3 [9.9] ms for the right and 48.2 [11.9] ms for the left) (p < 0.001, p < 0.001, p = 0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8 [53.8] vs. 78 [19.6] ms, p = 0.025) and the contralateral threshold during the attack (mean [SD] 143.8 [53.8] vs. 71.9 [14.1] ms, p = 0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r = 0.894, p < 0.001) and frequency of the attacks (r = 0.696, p = 0.004), but not correlated with photophobia. CONCLUSION: The VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus.

IVIg-induced headache: prospective study of a large cohort with neurological disorders.

BACKGROUND: Intravenous immune globulin (IVIg) is frequently used in some neurological diseases and is also the first-line therapy in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. We aimed to evaluate the frequency and characteristics of headaches, which is one of the most common side effects of IVIg treatment. METHODS: Patients who received IVIg treatment for neurological diseases were prospectively enrolled in 23 centers. Firstly, the characteristics of patients with and without IVIg-induced headaches were analyzed statistically. Then, patients with IVIg-induced headaches were classified into three subgroups determined by their history: no primary headache, tension-type headache (TTH), and migraine. RESULTS: A total of 464 patients (214 women) and 1548 IVIg infusions were enrolled between January and August 2022. The frequency of IVIg-related headaches was 27.37% (127/464). A binary logistic regression analysis performed with significant clinical features disclosed that female sex and fatigue as a side effect were statistically more common in the IVIg-induced headache group. IVIg-related headache duration was long and affected daily living activities more in patients with migraine compared to no primary headache and TTH groups (p = 0.01, respectively). CONCLUSION: Headache is more likely to occur in female patients receiving IVIg and those who develop fatigue as a side effect during the infusion. Clinicians' awareness of IVIg-related headache characteristics, especially in patients with migraine, may increase treatment compliance.

What to do with non-responders to CGRP(r) monoclonal antibodies: switch to another or move to gepants?

In this editorial we aim to provide potential therapeutic options in patients who do not benefit from treatment with CGRP(r) monoclonal antibodies. Based on current real-life studies and analysis of practical and economic aspects, we will analyze the potential benefits of changing CGRP-targeted treatment.

Medication overuse headache is associated with elevated lipopolysaccharide binding protein and pro-inflammatory molecules in the bloodstream.

OBJECTIVE: Medication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used analgesics worldwide and they are known to induce leaky gut. In this study, we aimed to investigate whether NSAID induced MOH is associated with altered circulating lipopolysaccharide binding protein (LBP) levels and inflammatory molecules. MATERIALS AND METHODS: Piroxicam (10 mg/kg/day, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain behavior was evaluated by periorbital withdrawal thresholds, head-face grooming, freezing, and head shake behavior. Serum samples and brain tissues were collected to measure circulating LBP, tight junction protein occludin, adherens junction protein vascular endothelial (VE)-cadherin, calcitonin gene-related peptide (CGRP), IL-6 levels and brain high mobility group box-1 (HMGB1) and IL-17 levels. RESULTS: Chronic piroxicam exposure resulted in decreased periorbital mechanical withdrawal thresholds, increased head-face grooming, freezing, and head shake behavior compared to vehicle administration. Serum LBP, CGRP, IL-6, IL-17, occludin, VE-cadherin levels and brain IL-17 and HMGB1 levels were significantly higher in piroxicam group compared to controls. Serum LBP was positively correlated with occludin (r = 0.611), VE-cadherin (r = 0.588), CGRP (r = 0.706), HMGB1 (r = 0.618) and head shakes (r = 0.921), and negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.740). CONCLUSION: Elevated serum LBP, VE-cadherin and occludin levels indicating disrupted intestinal barrier function and leakage of LPS into the systemic circulation were shown in female rats with MOH. LPS induced low-grade inflammation and elevated nociceptive and/or pro-inflammatory molecules such as HMGB1, IL-6, IL-17 and CGRP may play a role in the development and maintenance of MOH. Interference with leaky gut and pro-inflammatory nociceptive molecules could also be a target for sustained management of MOH.

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition.

BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

Reduced Short-Latency Afferent Inhibition Indicates Impaired Sensorimotor Integrity During Migraine Attacks.

BACKGROUND AND OBJECTIVE: Migraine attacks disrupt sensory information processing and may also disturb sensorimotor integration. This prospective pilot study aimed to assess the sensorimotor integration and inhibitory circuitry in the sensorimotor cortex using short-latency afferent inhibition (SAI) paradigm in migraine. METHODS: Twenty-five migraine without aura patients (10 interictal, 5 preictal, 10 ictal) and 16 healthy controls were enrolled. SAI was elicited by combining the right median nerve electrical stimulation and left motor cortical magnetic stimulation at the 21-millisecond interval. Mean motor evoked potential (MEP) amplitude ratio, recorded from right abductor pollicis muscle after single and conditioned stimulations, was calculated as SAI. RESULTS: Average MEP inhibition ratio after single and conditioned stimuli in healthy controls was not significantly different from interictal patients (45.1% ± 20.3% vs 44.5% ± 14.75% [P = .93]). However, SAI was significantly reduced during preictal/prodromal (-14.6% ± 42.8% [P = .002]) and ictal/headache (-7.4% ± 31.1% [P = .0001]) periods of migraine compared to healthy controls. CONCLUSION: Pronounced decrease in SAI during preictal and ictal periods in migraine was shown for the first time. Instead of inhibition to a conditioned stimulus, facilitation in the sensorimotor cortex was detected both ictally and preictally. Preictal SAI results suggest the presence of increased excitability state several hours prior to the headache phase. This phenomenon could be related to the cortical hyperresponsivity to sensory stimuli and cognitive disturbances accompanying migraine attacks as SAI is modulated by cholinergic activity.

Aura and Head pain: relationship and gaps in the translational models.

Migraine is a complex brain disorder and initiating events for acute attacks still remain unclear. It seems difficult to explain the development of migraine headache with one mechanism and/or a single anatomical location. Cortical spreading depression (CSD) is recognized as the biological substrate of migraine aura and experimental animal studies have provided mechanisms that possibly link CSD to the activation of trigeminal neurons mediating lateralized head pain. However, some CSD features do not match the clinical features of migraine headache and there are gaps in translating CSD to migraine with aura. Clinical features of migraine headache and results from research are critically evaluated; and consistent and inconsistent findings are discussed according to the known basic features of canonical CSD: typical SD limited to the cerebral cortex as it was originally defined. Alternatively, arguments related to the emergence of SD in other brain structures in addition to the cerebral cortex or CSD initiated dysfunction in the thalamocortical network are proposed. Accordingly, including thalamus, particularly reticular nucleus and higher order thalamic nuclei, which functions as a hub connecting the visual, somatosensory, language and motor cortical areas and subjects to modulation by brain stem projections into the CSD theory, would greatly improve our current understanding of migraine.

Behavioral and cognitive animal models in headache research.

Animal models have provided a growing body of information about the pathophysiology of headaches and novel therapeutic targets. In recent years, experiments in awake animals have gained attention as more relevant headache models. Pain can be assessed in animals using behavioral alterations, which includes sensory-discriminative, affective-emotional and cognitive aspects. Spontaneous behavioral alterations such as increased grooming, freezing, eye blinking, wet dog shake and head shake and decreased locomotion, rearing, food or water consumption observed during pain episodes are oftentimes easy to translate into clinical outcomes, but are giving little information about the localization and modality of the pain. Evoked pain response such as tactile and thermal hypersensitivity measures are less translatable but gives more insight into mechanisms of action. Mechanical allodynia is usually assessed with von Frey monofilaments and dynamic aesthesiometer, and thermal allodynia can be evaluated with acetone evaporation test and Hargreaves' test in animal models. Anxiety and depression are the most frequent comorbid diseases in headache disorders. Anxiety-like behaviors are evaluated with the open-field, elevated plus-maze or light/dark box tests. Interpretation of the latter test is challenging in migraine models, as presence of photophobia or photosensitivity can also be measured in light/dark boxes. Depressive behavior is assessed with the forced-swim or tail suspension tests. The majority of headache patients complain of cognitive symptoms and migraine is associated with poor cognitive performance in clinic-based studies. Cluster headache and tension type headache patients also exhibit a reversible cognitive dysfunction during the headache attacks. However, only a limited number of animal studies have investigated cognitive aspects of headache disorders, which remains a relatively unexplored aspect of these pathologies. Thus, the headache field has an excellent and growing selection of model systems that are likely to yield exciting advances in the future.

The effect of medial longitudinal arch height and medial longitudinal arch support insoles on postural balance in perimenopausal women

Background/aim: Changes in balance and postural control have been reported during the perimenopausal period. We investigated the effect of medial longitudinal arch height and medial arch support insoles on postural sway and balance in middle-aged perimenopausal women. Materials and methods: 29 women with normal arches and 29 women with low arches were included in the study. The foot arches of the participants were determined using the arch height index. The static balance index (SBI) measured by Kinesthetic Ability Trainer 3000 and functional reach test were used to evaluate postural balance. Measurements were obtained from all participants with and without medial arch support insoles. Results: The SBI-total scores without the insoles were found to be significantly higher in the lower arch group than in the normal arch group. SBI-total, SBI-anteroposterior, and SBI-mediolateral scores significantly improved in the low arch group in the presence of insoles, whereas the usage of insoles resulted in no difference in the normal arch group. In the presence of insoles, the reach distances to left and right sides increased in both groups, while the forward functional reach distances decreased. Conclusion: Medial longitudinal arch height and medial arch support insoles affect the balance parameters in perimenopausal women.

Analysis of mirror neuron system activation during action observation alone and action observation with motor imagery tasks.

This study aimed to explore the relationship between action observation (AO)-related corticomotor excitability changes and phases of observed action and to explore the effects of pure AO and concurrent AO and motor imagery (MI) state on corticomotor excitability using TMS. It was also investigated whether the mirror neuron system activity is muscle-specific. Fourteen healthy volunteers were enrolled in the study. EMG recordings were taken from the right first dorsal interosseous and the abductor digiti minimi muscles. There was a significant main effect of TMS timing (after the beginning of the movement, at the beginning of motor output state, and during black screen) on the mean motor evoked potential (MEP) amplitude. Mean MEP amplitudes for AO combined with MI were significantly higher than pure AO session. There was a significant interaction between session and TMS timing. There was no significant main effect of muscle on MEP amplitude. The results indicate that corticomotor excitability is modulated by different phases of the observed motor movement and this modulation is not muscle-specific. Simultaneous MI and AO enhance corticomotor excitability significantly compared to pure AO.

Visual and Postural Motion-Evoked Dizziness Symptoms Are Predominant in Vestibular Migraine Patients.

Background: Vestibular migraine (VM) is one of the most common underdiagnosed disorders. We aimed to study the clinical characteristics of VM patients who were referred to a neurology-headache unit by otolaryngology after exclusion of peripheral causes of vertigo. Methods: One hundred and one patients diagnosed with VM in the headache unit were included. Description of vestibular symptoms, demographic and clinical features, trigger factors, accompanying diseases, and response to vestibular-suppressant medications and prophylactic migraine treatment were evaluated. Results: Vestibular symptoms were triggered by daily head and body movements and mainly consisted of brief attacks lasting seconds (60.4% of patients) although the total duration of the vestibular episode lasted hours or days. Other aggravating factors were moving visual stimuli, passive motion, and visually busy environments. Visually induced vestibular symptoms were defined by 71.3% of the patients, and positional motion-induced vestibular symptoms were described by 82.2% of the patients. Vestibular symptoms were mainly defined as feeling the ground slipping from under their feet (40.6%), feeling like there is an earthquake or swaying (27.7%), sensation of rocking on a boat (26.7%), and sensation as if stepping on empty space (24.8%). The majority of the patients (83.2%) previously used vestibular-suppressant drugs, and these drugs were effective temporarily only in 12.9%. Conclusions: Chronic recurrent dizziness symptoms, rather than internal or external vertigo, are predominant in our VM patients. Recurrent brief dizziness attacks induced upon routine visual and/or postural motion, longstanding symptoms with limited response to vestibular suppressants, and precipitation by typical migraine triggers are suggestive of VM.

Cognitive dysfunction and migraine.

Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers. All of the clinical studies show poor cognitive performance during migraine attacks, though, the interictal data are conflicting. Migraineurs show impaired cognitive function interictally in most of the clinic-based studies. Population-based studies did not reveal a difference in cognitive functions between migraineurs and controls. The specific cognitive domains involved are information processing speed, basic attention, executive functions, verbal and non-verbal memory and verbal skills. Neurophysiological, imaging and pharmacological studies support clinical symptoms of cognitive impairment in migraine. Longitudinal studies do not suggest progressive cognitive decline over time in migraine patients. Preventive medications and comorbid disorders such as depression and anxiety can impact cognitive function, but cannot fully explain the cognitive impairment in migraine. In contrast to migraine, tension type or cluster headache are not associated with cognitive impairment, at least during headache-free periods.

Somatosensory temporal discrimination remains intact in tension-type headache whereas it is disrupted in migraine attacks.

Background and objective Somatosensory temporal discrimination was recently reported as prolonged during migraine attacks, which is consistent with disrupted sensorial perception in migraine. However, knowledge about central sensory processing in tension-type headache is still lacking. This prospective, controlled study aimed to investigate somatosensory temporal discrimination thresholds in tension-type headache. Methods The study included 10 tension-type headache patients, 10 migraine patients and 10 healthy volunteers without headache. Somatosensory temporal discrimination thresholds were evaluated during the headache attacks of tension-type headache and migraine patients. Results Somatosensory temporal discrimination thresholds of tension-type headache patients (39.0 ± 5.5 ms for the right hand and 40.6 ± 4.6 ms for the left hand) were significantly lower than those of episodic migraine patients (137.1 ± 35.8 ms for the right hand and 118.4 ± 34.3 ms for the left hand, p < 0.0001 and p < 0.0001 respectively), and comparable to those of healthy volunteers (38.6 ± 5.3 ms for the right hand and 38.3 ± 7.2 ms for the left hand, p = 0.79 and p = 0.45 respectively). Conclusion Central sensory processing, as tested by somatosensory temporal discrimination, was remarkably disrupted during the headache attacks in migraineurs, whereas it remained intact in the tension-type headache patients.

MR Tractography in Short Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Patients: Case Reports.

BACKGROUND: Short-lasting unilateral neuralgiform headache attack with conjunctival injection and tearing (SUNCT) is one of the trigeminal autonomic cephalalgias where neurovascular compression was detected in neuroimaging in recent years. CASE: We report two cases, a 52-year-old adult and a 69-year-old elderly patient with short-lasting and recurrent headache combined with cranial autonomic features. Diffusion tensor imaging (DTI) and magnetic resonance (MR) tractography of both patients outlined structural changes of the trigeminal nerve revealing neurovascular compression. Pain and autonomic symptoms were completely relieved in the 52-year-old patient who underwent microvascular decompression surgery. CONCLUSION: To our knowledge, this is the first time in the literature where MR tractography revealed structural changes in the trigeminal nerve secondary to neurovascular compression in SUNCT patients. We suggest that in SUNCT patients high-resolution magnetic resonance imaging (MRI) and/or DTI-MR tractography should be performed to exclude neurovascular compression. We propose that the compression of the trigeminal nerve could generate SUNCT symptoms and the posterior hypothalamus could be activated secondarily. With this point of view, trigeminal neuralgia and SUNCT could represent the different features of the neurovascular compression spectrum.

Chronic Migraine Is Associated With Sustained Elevation of Somatosensory Temporal Discrimination Thresholds.

BACKGROUND AND OBJECTIVE: Migraine headache attacks have been shown to be accompanied by significant prolongation of somatosensory temporal discrimination threshold values, supporting signs of disrupted sensorial processing in migraine. Chronic migraine is one of the most debilitating and challenging headache disorders with no available biomarker. We aimed to test the diagnostic value of somatosensory temporal discrimination for chronic migraine in this prospective, controlled study. METHODS: Fifteen chronic migraine patients and 15 healthy controls completed the study. Chronic migraine patients were evaluated twice, during a headache and headache-free period. Somatosensory temporal discrimination threshold values were evaluated in both hands. Duration of migraine and chronic migraine, headache intensity, clinical features accompanying headache such as nausea, photophobia, phonophobia and osmophobia, and pressure pain thresholds were also recorded. RESULTS: In the chronic migraine group, somatosensory temporal discrimination threshold values on the headache day (138.8 ± 21.8 ms for the right hand and 141.2 ± 17.4 ms for the left hand) were significantly higher than somatosensory temporal discrimination threshold values on the headache free day (121.5 ± 13.8 ms for the right hand and 122.8 ± 12.6 ms for the left hand, P = .003 and P < .0001, respectively) and somatosensory temporal discrimination thresholds of healthy volunteers (35.4 ± 5.5 ms for the right hand and 36.4 ± 5.4 ms for the left hand, P < .0001 and P < .0001, respectively). Somatosensory temporal discrimination threshold values of chronic migraine patients on the headache free day were significantly prolonged compared to somatosensory temporal discrimination threshold values of the control group (121.5 ± 13.8 ms vs 35.4 ± 5.5 ms for the right hand, P < .0001 and 122.8 ± 12.6 ms vs 36.4 ± 5.4 ms for the left hand, P < .0001). Somatosensory temporal discrimination threshold values of the hand contralateral to the headache lateralization (153.3 ± 13.7 ms) were significantly higher (P < .0001) than the ipsilateral hand (118.2 ± 11.9 ms) in chronic migraine patients when headache was lateralized. The headache intensity of chronic migraine patients rated with visual analog score was positively correlated with the contralateral somatosensory temporal discrimination threshold values. CONCLUSION: Somatosensory temporal discrimination thresholds persist elevated during the headache-free intervals in patients with chronic migraine. By providing evidence for the first time for unremitting disruption of central sensory processing, somatosensory temporal discrimination test stands out as a promising neurophysiological biomarker for chronic migraine.

Distinct Food Triggers for Migraine, Medication Overuse Headache and Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is an under-diagnosed common health problem that impairs quality of life. Migraine and IBS are comorbid disorders that are triggered by foods. We aim to investigate IBS frequency in medication overuse headache (MOH) patients and identify food triggers and food avoidance behavior. METHODS: Participants who completed the cross-sectional, observational and online survey were included (n = 1118). Demographic data, comorbid disorders, medications used, presence of headache, the diagnostic features of headache and IBS, migraine related subjective cognitive symptoms scale (MigSCog), consumption behavior of patients regarding 125 food/food additives and food triggers were asked about in the questionnaire. RESULTS: Migraine and MOH diagnoses were made in 88% and 30.7% of the participants, respectively. Non-steroidal anti-inflammatory drugs (NSAIDs) were the main overused drug (89%) in MOH patients. IBS symptoms were present in 35.8% of non-headache sufferers, 52% of migraine patients and 65% of MOH patients. Specific food triggers for MOH patients were dopaminergic and frequently consumed as healthy foods such as banana, apple, cherry, apricot, watermelon, olive, ice cream and yogurt. MigSCog scores were significantly higher in episodic migraine and MOH patients when IBS symptoms coexisted. CONCLUSIONS: The frequency of IBS was higher in MOH patients compared to migraine patients. Coexistence of IBS seems to be a confounding factor for cognitive functions. MOH specific triggers were mostly dopaminergic foods, whereas migraine specific food triggers were mostly histaminergic and processed foods. Personalized diets focusing on food triggers and interference with leaky gut must be integrated to MOH and migraine treatment to achieve sustainable management of these disorders.