Efficacy of a dual task protocol on neurophysiological and clinical outcomes in migraine: a randomized control trial.

The main aim of this study was to investigate the efficacy of a dual task protocol in people with episodic migraine with respect to both active exercises only and cognitive task only treatments, concerning some neurophysiological and clinical outcomes. A randomized control trial was adopted in people with episodic migraine without aura. Some neurophysiological and clinical outcomes were collected (t0): resting motor threshold (rMT), short intracortical inhibition (SICI) and facilitation (ICF), pressure pain threshold (PPT), trail making test (TMT), frontal assessment battery (FAB), headache-related disability (MIDAS) and headache parameters. Then, participants were randomized into three groups: active exercise only (n = 10), cognitive task only (n = 10) and dual task protocol (n = 10). After 3 months of each treatment and after 1-month follow-up the same neurophysiological and clinical outcomes were revaluated. A significant time x group effect was only found for the trapezius muscle (p = 0.012, pη2 = 0.210), suggesting that PPT increased significantly only in active exercise and dual task protocol groups. A significant time effect was found for rMT (p < 0.001, pη2 = 0.473), MIDAS (p < 0.001, pη2 = 0.426), TMT (p < 0.001, pη2 = 0.338) and FAB (p < 0.001, pη2 = 0.462). A repeated measures ANOVA for SICI at 3 ms highlighted a statistically significant time effect for the dual task group (p < 0.001, pη2 = 0.629), but not for the active exercises group (p = 0.565, pη2 = 0.061), and for the cognitive training (p = 0.357, pη2 = 0.108). The dual task protocol seems to have a more evident effect on both habituation and sensitization outcomes than the two monotherapies taken alone in people with migraine.

Differences in musculoskeletal dysfunctions and in postural alterations between chronic migraine and chronic tension type headache: A cross-sectional study.

OBJECTIVE: The aim of present study is to assess postural alterations and musculoskeletal dysfunctions over all spine in patients with chronic migraine and chronic tension type headache, moreover to highlight the differences between these two forms of primary headache. METHODS: A Cross sectional study was adopted to evaluate the musculoskeletal profile in patients with chronic migraine and with chronic tension type headache. The Bio photogrammetric evaluation was performed using the postural assessment software PAS/SAPO, while unilateral passive accessory intervertebral motion (PAIMs) were applied for manual examinations of spine segments from C0 to L5 vertebra. The One-way Analysis of Variance (ANOVA) test was used to compare the three groups with the software GraphPad InStat 3.06. RESULTS: A total of 60 patients were recruited, 20 for chronic tension type group, 20 for chronic migraine group and 20 healthy controls. The most interesting findings was that patients with chronic primary headaches presented postural alterations in all parameters (cranio-vertebral angle and lumbar-pelvic angle) and musculoskeletal dysfunctions in all spine with respect to healthy controls. Finally, the most clinically relevant finding was that no differences were found between chronic migraine and chronic tension type headache concerning the postural alterations nor the musculoskeletal dysfunctions. CONCLUSION: The sensitization acts as a substrate or consequence of these musculoskeletal dysfunctions in chronic primary headache. Therefore, non-pharmacological treatments targeted in the musculoskeletal system may be a good option in the management of chronic primary headache, especially when these therapies integrate various techniques that involve all spine.

Instrumental assessment of pressure pain threshold over trigeminal and extra-trigeminal area in people with episodic and chronic migraine: a cross-sectional observational study.

BACKGROUND: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. METHODS: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). RESULTS: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. CONCLUSIONS: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.

Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function. METHODS: A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery. RESULTS: Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles ( P < 0.001), lower resting motor threshold (-10.5% of the stimulator output, 95% CI: -16.8 to -4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (-1.1, 95% CI: -1.7 to -0.5, P = 0.001, Cohen d = 0.915). CONCLUSIONS: Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.

BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.

Validation of the Italian version of the Cluster Headache Impact Questionnaire (CHIQ).

BACKGROUND: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. METHODS: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach's alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman's correlation coefficient. RESULTS: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. CONCLUSION: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research.

Skin wetness sensitivity across body sites commonly affected by pain in people with migraine.

OBJECTIVE: The objective of this study was to evaluate skin wetness perception and thermal sensitivity in people with migraine and similar healthy controls. BACKGROUND: Environmental triggers, such as cold and humidity, are known triggers for pain in people with migraine. Sensory inputs might be implicated in such heightened responses to cold-humid environments, such that a migraine-induced hypersensitivity to cold wetness could be present in people with migraine. However, we lack empirical evidence on skin thermal and wetness sensitivity across skin sites commonly associated with reported pain in migraine, such as the forehead. METHODS: This prospective cross-sectional observational study, conducted in a university hospital setting, evaluated skin wetness perceptions and thermal sensations to wet non-noxious warm-wet, neutral-wet, and cold-wet stimuli applied to the forehead, the posterior neck, and the index finger pad of 12 patients with migraine (mean and standard deviation for age 44.5 ± 13.2 years, 7/12 [58%] women) and 36 healthy controls (mean and standard deviation for age 39.4 ± 14.6 years, 18/36 [50%] women). RESULTS: On the forehead, people with migraine reported a significantly higher wetness perception than healthy controls across all thermal stimulus (15.1 mm, 95% confidence interval [CI]: 1.8 to 28.5, p = 0.027, corresponding to ~ 15% difference), whereas no significant differences were found on the posterior neck nor on the index finger pad. We found no differences among groups in overall thermal sensations (-8.3 mm, 95% CI: -24.0 to 7.3, p = 0.291; -7.8 mm, 95% CI: -25.3 to 9.7, p = 0.375; and 12.4 mm, 95% CI: -4.0 to 28.9, p = 0.133; forehead, posterior neck, and index finger, respectively). CONCLUSION: These findings indicate that people with migraine have a heightened sensitivity to skin wetness on the forehead area only, which is where pain attacks occur. Future studies should further explore the underlying mechanisms (e.g., TRPM8-mediated cold-wet allodynia) that lead to greater perception of wetness in people with migraine to better understand the role of environmental triggers in migraine.

Algometer Assessment of Pressure Pain Threshold After Onabotulinumtoxin-A and Physical Therapy Treatments in Patients With Chronic Migraine: An Observational Study.

The purpose of this study was to evaluate pain hypersensitivity in chronic migraine patients 3 months after undergoing onabotulinumtoxin-A therapy, physical therapy (PT), or the combination of the two. Pressure pain threshold (PPT) was assessed in accordance with Andersen's guidelines, focusing on five muscles in the trigeminocervical area (namely, trapezius, levator scapulae, temporalis, sub-occipitalis, and scalenus medius) and one muscle outside of the area, (i.e., tensor fasciae latae). Moreover, three headache parameters, namely, attack frequency, duration, and pain intensity, were recorded in an ad hoc diary kept by the patients. A total of 30 patients were included in three treatment groups: 1. onabotulinumtoxin-A therapy, 2. PT, and 3. a combination of onabotulinumtoxin-A and PT. The results show that, at the final assessment, the PPT was significantly reduced in the combined treatment group compared to the two single-therapy groups. As regards headache parameters, frequency and duration of the attacks were decreased significantly in all three treatment groups, whereas in pain intensity, the reduction was statistically significant in the combined treatment group and the onabotulinumtoxin-A therapy. Results suggest that a better pain modulation in patients with chronic migraine can be achieved with a combined treatment of onabotulinumtoxin-A and physical therapy. Indeed, the combination of both pharmacological and non-pharmacological treatments results in the reduction of both headache-related parameters and widespread pressure hyperalgesia.

Lifestyle impact on migraine during home confinement.

BACKGROUND: The COVID-19 lockdown has influenced people lifestyle, behaviour, physical activity (PA), and working habits as well as, possibly, migraine. The aim of the study was to assess the impact of lockdown on the burden of migraine attacks during COVID-19 lockdown. METHODS: Patients were interviewed, and data about demographics, PA, daily behaviour, working habits, disability (HIT-6) and characteristics of migraine and drugs consumption were compared between the first month of the lockdown in Italy (March 2020), and a reference month prior the lockdown (January 2020). RESULTS: 37 patients were analysed, classified as migraine without aura (MwoA) (n = 26) and migraine with aura (MwA) plus migraine with and without aura (MwA/MwoA) (n = 11). During the lockdown, a greater proportion of patients with insufficient PA (65% vs 31%; p = 0.012) were found. Reduced mean headache duration [3 h, (2-12) vs 2 h (1-8); p = 0.041] and HIT score [59 (51-63) vs 50 (44-57); p = 0.001] were found in MwoA patients during the lockdown, while no changes found in patients with MwA + MwA/MwoA. CONCLUSIONS: Lockdown induced significant changes in PA and working habits of people with migraine and was found to be associated with improved migraine-related symptoms which might depend by different lifestyle habits.

Instrumental assessment of physiotherapy and onabolulinumtoxin-A on cervical and headache parameters in chronic migraine.

INTRODUCTION: The purpose of the present study is to compare the effect of the physiotherapy to onabolulinumtoxin-A, and their combination, in relation to cervical and headache parameters in patients with chronic migraine. METHODS: This is an observational cohort study conducted by a headache center and a physiotherapy degree course on 30 patients with chronic migraine. The patients were distributed in three groups of treatments for three months: onabolulinumtoxin-A only, physiotherapy only, and onabolulinumtoxin-A plus physiotherapy. The patients were evaluated, before and after each treatment, using the following: the postural assessment software SAPO for the forward head posture; the CROM goniometer for the cervical range of motion; the Migraine Disability Assessment Score for headache parameters. RESULTS: After 3 months of each treatment, the scores obtained for the headache-related disability and the frequency of migraine decreased significantly for all groups, but the pain intensity scores changed significantly only in the onabolulinumtoxin-A (p = 0.01) and in the onabolulinumtoxin-A plus physiotherapy groups (p = 0.007). On the other hand, the forward head posture was reduced significantly in the physiotherapy (p = 0.002) and in the onabolulinumtoxin-A plus physiotherapy groups (p = 0.003). The cervical range of motion increased significantly in certain directions in the physiotherapy group and in the onabolulinumtoxin-A plus physiotherapy groups. CONCLUSIONS: The physiotherapy improved the cervical parameters. The onabolulinumtoxin-A decreased pain intensity. As a consequence, it can be said that the combined treatment was more useful than a mono-therapy alone. From our results, it can be concluded that onabolulinumtoxin-A plus physiotherapy could be a good option in the management of chronic migraine.

Lost diagnoses in not otherwise specified headache in Emergency Department.

 The diagnosis of Not Otherwise Specified (NOS) headaches in the Emergency Department (ED) is frequent despite many specialist visits performed. The aim of the study was to examine specialist visits carried out in the patients discharged from ED with diagnosis of NOS headache to evaluate discrepancies between specialist and ED diagnosis at discharge. We retrospectively (1.6.2018-31.12.2018) analyzed all the patients admitted with non-traumatic headache to the ED of the tertiary-care University Hospital of Trieste. We evaluated the patients discharged from ED with a final diagnosis of NOS headache and who underwent at least one specialist examination. Demographic data, specialist and ED diagnosis were analyzed.  One hundred twenty-four patients (93 F, 31 M, mean age 44 ± 15 years) were included. 71.8% of patients were examined only by a neurologist, 12.9% by non-neurologists, 15.3% by both neurologist and non-neurologist. Only 37% of the patients received a precise diagnosis. Neurologist made a diagnosis slightly more frequently than the other consultants (40.5% vs 37.5%). Neurologists diagnosed primary headaches, headaches secondary to neurological diseases, and facial neuralgia, instead non-neurologists diagnosed only headaches secondary to non-neurological diseases. Primary headaches were diagnosed in 25.7% of cases, migraine being the most frequent. Physicians did not report any specialist diagnoses in the ED discharge sheet. Specialist consultants made specific diagnoses in about one-third of patients that were not reported as final in the discharge records by the ED physician. This leads to a loss of diagnoses and to an overestimation of NOS headache.

COVID-19 lockdown attack on headache emergency admissions: a multidisciplinary retrospective study.

BACKGROUND: During the first COVID-19 lockdown in Italy, it was observed a reduction in emergency department (ED) attendances due to non-SARS-COV-2-related acute/chronic conditions. OBJECTIVE: To analyze the impact of the COVID-19 lockdown on patients reporting headache as the principal presenting symptom on admission to the ED of the tertiary care University Hospital of Trieste over the relevant period. METHODS: We retrospectively evaluated the frequency, features, and management of ED attendances for headache during the COVID-19 lockdown from 8 March to 31 May 2020, comparing it with the pre-lockdown period (January-February 2020) and the first 5 months of 2019. RESULTS: A reduction in ED total attendances was observed in the first 5 months of 2020 compared to the same period in 2019 (21.574 and 30.364, respectively; - 29%), in particular with respect to headache-related attendances (174 and 339 respectively; - 49%). During the COVID-19 lockdown, it was recorded a minor reduction in the ED access rate of female patients (p = 0.03), while no significant variation was detected in repeaters' prevalence, diagnostic assessment, and acute treatment. The ratio of not otherwise specified, secondary, and primary headaches (48.4%, 30.6%, and 21.0% respectively) remained unchanged during the COVID-19 lockdown, in comparison to the control periods. CONCLUSION: The COVID-19 pandemic impacted the number of ED attendances for headache but not their management and setting. Despite a reduction of accesses for headache due to the pandemic emergency, the distribution of headache subtypes and the rate of repeaters did not change.

A novel computed tomography perfusion-based quantitative tool for evaluation of perfusional abnormalities in migrainous aura stroke mimic.

BACKGROUND: Migrainous aura (MA) represents the third most common stroke mimic (SM). Advanced neuroimaging is pivotal in the assessment of patients with focal neurological acute symptoms. We investigated brain perfusion alterations in MA-SM patients using a novel CT perfusion (CTP)-based quantitative approach in order to improve differential diagnosis between MA and acute stroke. METHODS: We processed and analysed the clinical and neuroimaging CTP data, acquired within 4.5 h from symptom onset, of patients with acute focal neurological symptoms receiving a final diagnosis of MA. The differences between ROI, compatible with MA symptoms, and contralateral side were automatically estimated in terms of asymmetry index (AI%) by the newly developed tool for mean transit time (MTT), CBF, and cerebral blood volume (CBV) CTP parameters. The AI% ≥ 10% was considered significant. RESULTS: Out of 923 admitted patients, 14 patients with MA were included. In 13 out of 14 cases, a significant pattern of hypoperfusion was observed by quantitative analysis in at least one of the CTP maps. In 7 patients, all three CTP maps were significantly altered. In particular, MTT-AI% increased in 11 (79%) cases, while CBF-AI% and CBV-AI% decreased in 12 (86%) and in 9 (64%) patients, respectively. All CBV values were above ischemic stroke core threshold and all MTT-AI were below ischemic penumbra threshold. CONCLUSIONS: Our data suggest that a novel CTP-quantitative approach may detect during MA a moderate hypoperfusion pattern in the cerebral regions compatible with aura symptoms. The use of this novel tool could support differential diagnosis between MA and acute stroke.

Adherence to guidelines of treatment of non-traumatic headache in the emergency department.

To evaluate therapies employed in patients presenting to the emergency department (ED) with a chief complaint of non-traumatic headache to check if guidelines are followed. A 6-month retrospective analysis of the ED records of all the patients who referred to the ED of the University Hospital of Trieste for non-traumatic headache was performed. Out of 37.335 admissions, 336 patients were selected (0.9%). Diagnosis at discharge was primary headache (25.6%), secondary headache (40.5%), and headache "not otherwise specified" (33.9%). One-hundred-ninety-three patients were treated in mono- (51.8%) or poly-therapy (48.2%), with NSAIDs (46.5%), benzodiazepines (13.4%), antiemetics (10.7%), analgesics (8.3%), opioids (1.6%), triptans (1.5%), and other drugs (17.7%). NSAIDs, particularly ketorolac, are the class of drugs most often prescribed in ED, independently of the discharge diagnosis. Metoclopramide is rarely used in monotherapy (4%), but it is the drug most frequently used in association with NSAIDs (19.3%). Only two migraineurs received triptans. Mean time spent in ED was 231 ± 130 min, which was significantly longer in patients who received treatment (272 ± 141 vs. 177 ± 122 min; p = 0.003). No drugs had any side effects. In accordance with the current guidelines, NSAIDs monotherapy or in association with antiemetics were the drugs most often prescribed in ED. Opioids were rarely used probably because of potential sedative side effects. Only very few patients received triptans. Special attention should be drawn also in ED to apply the International Classification of Headache Disorders criteria, which can lead to clarify the diagnosis and receive the specific treatment.

Osteopathic Manipulative Therapy in Patients With Chronic Tension-Type Headache: A Pilot Study.

CONTEXT: Nonpharmacologic treatment, such as osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) may be a beneficial complementary treatment for tension-type headache. However, to the authors' knowledge, the benefit of OMTh in the management of tension-type headache has not been explored, especially chronic tension-type headache (CTTH). OBJECTIVE: To investigate the effectiveness of OMTh compared with traditional treatment in reducing pain intensity, frequency, and duration of CTTH, and to evaluate the objective postural measurement of the forward head posture (FHP) as an integral parameter in the assessment of the effects of OMTh and traditional management of CTTH. METHODS: Patients with CTTH were registered at the Headache Centre of Trieste in Italy. At the time of the study, none of the patients had been taking any headache prophylaxis in the past 3 months. A 3-month baseline period was recorded by all patients with an ad hoc diary. Patients were randomly placed in the test or control group using a simple randomization program in Excel (Microsoft). Patients in the OMTh group underwent a 3-month period of OMTh, and patients in the control group were treated with amitriptyline. Pain intensity, frequency, and duration of headaches, as well as FHP were analyzed. RESULTS: The study enrolled 10 patients (mean [SD] age, 42.6 [15.2] years) in the OMTh group and 10 patients (51.4 [17.3] years) in the control group. The final assessment of OMTh patients showed statistically significant changes in all headache parameters: pain intensity decreased from a mean (SD) score of 4.9 (1.4) to 3.1 (1.1) (P=.002); frequency decreased from 19.8 (6) to 8.3 (6.2) days per month (P=.002); and the duration of headaches decreased from 10 (4.2) to 6 (3) hours (P=.01). Significant improvement of all parameters was found in the control group as well: pain intensity decreased from a mean (SD) score of 5.9 (0.7) to 4.2 (1.75) (P=.03); frequency decreased from 23.4 (7.2) to 7.4 (8.7) days per month (P=.003); and duration decreased from 7.8 (2.9) to 3.6 (2.1) hours (P=.002). Forward head posture significantly improved in OMTh patients (P=.003). CONCLUSIONS: Our data suggested that OMTh may be an effective treatment to improve headaches in patients with CTTH. Our results also suggest that OMTh may reduce FHP.

Dramatic placebo effect of high frequency repetitive TMS in treatment of chronic migraine and medication overuse headache.

Chronic migraine (CM) is often associated with medication overuse headache (MOH). Few small trials have been conducted on Transcranial Magnetic Stimulation for CM treatment, but results are conflicting. Aim of the study was to investigate the effects of high frequency of repetitive Transcranial Magnetic Stimulation (hf-rTMS) in the dorsolateral prefrontal cortex combined with strongly suggesting to avoid medications overuse in patients suffering with CM and MOH. A six-month single-centre perspective randomized double-blinded study was conducted at the Headache Centre of Trieste. Patients suffering with CM and MOH were randomly enrolled in two groups to receive active hf-rTMS in DLPFC or sham hf-rTMS. Headache days (HD), headache hours (HH) and symptomatic drug intake (SDI) were recorded for 30 days before the beginning of stimulation (T0) and during the three following months (T3). Disability (MIDAS score) was evaluated at T0 and at the three-month follow-up visit. The primary outcome was the evaluation of reduction of HD. Reduction of SDI, HH and disability were considered as secondary outcomes. Out of 26 patients enrolled, 14 completed the study, 7 underwent hf-rTMS and 7 sham-TMS. There were no significant differences between groups at T0 in demographic data and headache measures. Mean number of HD, HH, SDI, and MIDAS similarly reduced in the two groups. Our study failed in demonstrating that hf-rTMS with detoxification advice could be better than detoxification advice alone in CM treatment. hf-rTMS carries a high potential of inducing placebo effect and this can be usefully leveraged to enhance patients' coping strategies.

Rare primary headaches in Italian tertiary Headache Centres: Three year nationwide retrospective data from the RegistRare Network.

Background Rare primary headaches are mainly included in Chapters 3, Trigeminal autonomic cephalalgias, and 4, Other primary headache disorders, Part One of the International Classification of Headache Disorders 3rd edition. Epidemiological data are scarce, mostly emerging from case series or small studies, with the exception of cluster headache. In order to overcome the knowledge gap about rare primary headaches, the RegistRare Network was launched in 2017 to promote research in the field. Methods A retrospective cohort study including patients who, from April 30, 2014 to May 1, 2017, visited seven Italian tertiary Headache Centres, was undertaken to estimate in that clinical setting prevalence and incidence of headaches included in Chapters 3 and 4, Part One of the International Classification of Headache Disorders 3rd edition. Prevalent headache is defined as a headache recorded within the study timeframe, regardless of when the diagnosis was made. Incident headache is defined as a headache diagnosed for the first time in the patient during the study period. Results Twenty thousand and eighty-three patients visited the participating centres, and 822 (4.1%) prevalent cases, of which 461 (2.3%) were incident cases, were registered. Headaches listed in Chapter 3 affected 668 patients, representing 81.3% of the total number of prevalent cases. Headaches listed in Chapter 4 affected 154 patients and represent 18.7% of the total number of prevalent cases. Cluster headaches represent the most frequently diagnosed rare headaches (70.4%). For 13 entities out of 20, no cases were registered in more than 50% (n ≥ 4) of the centres, and for 14 entities more than 50% of diagnoses were incident. Conclusions This large, multicentre study gives the first wide-ranging snapshot of the burden in clinical practice of rare headaches and confirms that cooperative networks are necessary to study rare headaches, as their prevalence is often very low. The launch of a disease registry by the RegistRare Network will favour research in this neglected population of headache patients. Trial registration NCT03416114.

Migrainous aura as stroke-mimic: The role of perfusion-computed tomography.

OBJECTIVES: The acute-onset of migrainuos aura (MA) can be erroneously diagnosed in Emergency Department (ED) as acute stroke (AS) and it can be classified as "stroke mimic" (SM). Perfusion computer tomography (PCT) may be useful to improve detection of infarcts. The aim of the study was to investigate the role in ED of PCT in improving diagnosis of migrainous aura. Data were compared with the well-defined perfusion patterns in patients with acute ischemic stroke. PATIENTS AND METHODS: A standardized Stroke Protocol was planned. The protocol consisted in centralizing in ED all the patients with acute-onset of neurological symptoms compatible with cerebrovascular disease and in performing a general and neurological examination, hematological tests, brain non-contrast computed tomography (NCCT), CT angiography (CTA) of the supra-aortic and intracranial arteries and cerebral PCT. Patients with diagnosis of definite or probable acute stroke were hospitalized in Stroke Unit (SU). A six-months retrospective analysis of all the patients included in the Stroke Protocol and discharged from ED or from SU with a diagnosis of migraine with aura was performed. RESULTS: 172 patients were included in the Stroke Protocol and 6 patients were enrolled. NCCT, CTA and PCT were performed after 60-90 min from symptoms onset and revealed normal perfusion. Intravenous thrombolysis was performed only in one patient. CONCLUSION: Patients with acute-onset of neurological symptoms, who have rapid progressive improvement of symptoms, normal neuroimaging, in particular PCT, and preceding episodes of migraine with aura, may be considered as suffering from MA. In these cases, even if thrombolysis is safe, clinicians may defer a prompt aggressive treatment.

The reappearance of hemiplegic cluster headaches: A case report and review of the literature.

Cluster headache (CH) is a rare and severe syndrome characterized by the recurrence of unilateral pain attacks, of short duration (15-180min), and associated with ipsilateral cranial autonomic symptoms. Although, not formally included in the International Classification of Headache Disorders, hemiplegic cluster headache (HCH) is an even more rare subtype of CH in which typical attacks can be accompanied by visual, sensory, and/or aphasic migrainous auras that have a variable propensity to evolve in reversible hemi-motor symptoms. After its first description in 2002, only few cases of HCH have been reported and many open questions about its prevalence and pathophysiology still need to be addressed. We describe a case of a 41-year old male that fulfilled the ICHD criteria for episodic CH who experienced atypical attacks characterized by concomitant acute onset of sensory aura, aphasia and hemi-motor symptoms. We also provide a concise review of the available literature and discuss the prevalence and the possible pathogenesis of CH with hemiplegic features.

Case Report: Coexistence of SUNCT and Hypnic Headache in the Same Patient.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co-occurrence have been described so far. CASE RESULTS: A 49-year-old woman who has been suffering from SUNCT for years, with alternation of symptomatic periods and remissions, developed a new headache with different clinical features, presenting exclusively during sleep and with a dramatic responsiveness to caffeine, that met the diagnostic criteria for HH. CONCLUSIONS: The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism.