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Background: Spinal CSF leak can cause disabling headaches and neurological symptoms. Lack of awareness, diagnostic delay and treatment inconsistencies affect the quality of CSF leak care globally. This is the first study aiming to identify and assess these challenges in Canada., Methods: A cross-sectional online survey of Canadian patients with spinal CSF leak was designed in collaboration with Spinal CSF Leak Canada, including questions on demographics, headache condition, investigations, treatments, quality of life, financial consequences and out-of-country care., Results: The survey captured 103 respondents with confirmed spinal CSF leak diagnosis, of whom 56% were still suffering. The majority were female (80%), most being highly educated, with a mean age of 41.8 (SD: 10.37) years at the time of diagnosis. Inconsistencies in care resulted in variable durations for obtaining diagnosis and treatment. The majority of respondents (88%) had seen multiple physicians, and only 50% had seen a CSF leak specialist. Invasive imaging was not performed in 43%. CSF leak relapse after initial successful treatment occurred frequently (43%). The incidence of rebound intracranial hypertension was high (52.5%), and the treatment was difficult to access (77%). Out-of-country care was common (28%), and the impact on financial health was omnipresent (81.5%)., Conclusion: The survey demonstrates significant gaps in spinal CSF leak care in Canada, similar to global observations. Lack of awareness and access, delayed care, and inconsistencies in investigations and management are common. Spinal CSF leak significantly impacts patients' physical, mental and financial well-being. Increased awareness, referral pathways and standardized treatment algorithms are key factors in optimizing patient care in Canada.

Objective: We have updated the migraine prevention guideline of the Canadian Headache Society from 2012, as there are new therapies available, and additionally, we have provided guidelines for the prevention of chronic migraine, which was not addressed in the previous iteration., Methods: We undertook a systematic review to identify new studies since the last guideline. For studies identified, we performed data extraction and subsequent meta-analyses where possible. We composed a summary of the evidence found and undertook a modified Delphi recommendation process. We provide recommendations for treatments identified and additionally expert guidance on the use of the treatments available in important clinical situations., Results: We identified 61 studies that were included in this evidence update and identified 16 therapies we focused on. The anti-calcitonin gene-related peptide (CGRP) agents were approved by Health Canada between 2018 and 2024 and provide additional options for episodic and chronic migraine prevention. We also summarize evidence for the use of propranolol, topiramate and onabotulinumtoxinA in addition to anti-CGRP agents as treatments for chronic migraine. We have downgraded topiramate to a weak recommendation for use and gabapentin to a weak recommendation against its use in episodic migraine. We have weakly recommended the use of memantine, levetiracetam, enalapril and melatonin in episodic migraine., Conclusion: Based on the evidence synthesis, we provide updated recommendations for the prevention of episodic and chronic migraine utilizing treatments available in Canada. We additionally provided expert guidance on their use in clinical situations.

Objective: To describe demographic and clinical characteristics, healthcare resource use, costs, and treatment patterns in three migraine cohorts., Methods: This retrospective observational study using administrative data examined patients with episodic migraine (EM), chronic migraine (CM) (without medication overuse headache [MOH]), and medication overuse headache in Alberta, Canada. Migraine patients were identified between 2012 and 2018 based on ≥ 1 diagnostic codes or triptan prescription. Patients with CM were defined using parameter estimates of a logistic regression model, and MOH was defined as patients with an average of ≥ 15 supply days covered of acute medications. EM was defined as patients without CM or MOH. Study outcomes were summarized using descriptive statistics., Results: Patients with EM (n = 144,574), CM (n = 27,283), and MOH (n = 11,485) were included. Higher rates of healthcare use and costs were observed for CM (mean [SD] all-cause cost: ($12,693 [40,664]) and MOH ($16,611.5 [$38,748]) versus episodic migraine ($4,251 [$40,637]). Across all cohorts, opioids were the most dispensed acute medication (range across cohorts: 31.7%-89.8%), while antidepressants and anticonvulsants were the most dispensed preventive medication. Preventative medication classes were used by a minority of patients in each cohort, except anticonvulsants, where 50% of medication overuse patients had a dispensation., Conclusions: Patients with CM and MOH have a greater burden of illness compared to patients with EM. The overutilization of acute medication, particularly opioids, and the underutilization of preventive medications highlight an unmet need to more effectively manage migraine.

Background: Migraine poses a significant burden worldwide; however, there is limited evidence as to the burden in Canada. This study examined the treatment patterns, healthcare resource use (HRU), and costs among newly diagnosed or recurrent patients with migraine in Alberta, Canada, from the time of diagnosis or recurrence., Methods: This retrospective observational study utilized administrative health data from Alberta, Canada. Patients were included in the Total Migraine Cohort if they had: (1) ≥1 International Classification of Diseases diagnostic code for migraine; or (2) ≥1 prescription dispense(s) for triptans from April 1, 2012, to March 31, 2018, with no previous diagnosis or dispensation code from April 1, 2010, to April 1, 2012., Results: The mean age of the cohort (n = 199,931) was 40.0 years and 72.3% were women. The most common comorbidity was depression (19.7%). In each medication class examined, less than one-third of the cohort was prescribed triptans and fewer than one-fifth was prescribed a preventive. Among patients with ≥1 dispense, the mean rate of opioid prescriptions was 4.61 per patient-year, compared to 2.28 triptan prescriptions per patient-year. Migraine-related HRU accounted for 3%-10% of all use., Conclusion: Comorbidities and high all-cause HRU were observed among newly diagnosed or recurrent patients with migraine. There is an underutilization of acute and preventive medications in the management of migraine. The high rate of opioid use reinforces the suboptimal management of migraine in Alberta. Migraine management may improve by educating healthcare professionals to optimize treatment strategies.

Background: Trigeminal autonomic cephalalgias (TACs) are a group of highly disabling primary headache disorders. Although pharmacological treatments exist, they are not always effective or well tolerated. Occipital nerve stimulation (ONS) is a potentially effective surgical treatment., Objective: To perform a systematic review of the efficacy of ONS in treating TACs., Methods: A systematic review was performed using Medline, Embase, and Cochrane databases. Primary outcomes were reduction in headache intensity, duration, and frequency. Secondary outcomes included adverse event rate and reduction in medication use. Because of large differences in outcome measures, data for patients suffering from short-lasting, unilateral, and neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and cranial autonomic symptoms (SUNA) were reported separately. Risk of bias was assessed using the NIH Quality Assessment Tools., Results: A total of 417 patients from 14 published papers were included in the analysis, of which 15 patients were in the SUNCT/SUNA cohort. The mean reduction in headache intensity and duration was 26.2% and 31.4%, respectively. There was a mean reduction in headache frequency of 50%, as well as a 61.2% reduction in the use of abortive medications and a 31.1% reduction in the use of prophylactic medications. In the SUNCT/SUNA cohort, the mean decrease in headache intensity and duration was 56.8% and 42.8%. The overall responder rate, defined as a >50% reduction in attack frequency, was 60.8% for the non-SUNCT/non-SUNA cohort and 66.7% for the SUNCT/SUNA cohort. Adverse events requiring repeat surgery were reported in 33% of cases. Risk of bias assessment suggests that articles included in this review had reasonable internal validity., Conclusion: ONS may be an effective surgical treatment for approximately two thirds of patients with medically refractory TACs., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: This study seeks to determine the prevalence and nature of cannabis use in patients with headache in a tertiary headache clinic and to explore patients' empiric experience in using cannabinoids therapeutically., Background: Many patients with headache report cannabinoid use as an effective abortive and/or preventive therapy. Mounting evidence implicates cannabinoids in pain mechanisms pertaining to migraine and other headache types., Methods: A cross-sectional study surveyed 200 patients presenting with any headache disorder to a tertiary headache clinic in Calgary, Alberta. Descriptive analyses were applied to capture information about headache diagnoses and the frequency, doses and methods of cannabinoid delivery employed, as well as patients' perceptions of therapeutic benefit and selected negative side effects., Results: Active cannabinoid users comprised 34.0% of respondents. Approximately 40% of respondents using cannabinoids engaged in very frequent use (≥300 days/year). Of cannabinoid modalities, liquid concentrates were most popular (39.2%), followed by smoked cannabis (33.3%). Patients endorsed cannabinoid use for both prevention and acute therapy of headaches, often concurrently. Sixty percent of respondents felt cannabinoids reduced headache severity, while 29.2% perceived efficacy in aborting headaches. Nearly 5% of respondents volunteered that they had encountered a serious problem such as an argument, fight, accident, or work issue as a result of their cannabis use. Approximately 35.4% of users had attempted to reduce their use., Conclusion: This survey shows that over one-third of patients with headache disorders in a tertiary headache clinic use cannabis as a treatment for their headaches. Of these, about 25% and 60% perceive improvements in headache frequency and severity, respectively. The results of this survey will aid neurologists and headache specialists in understanding the landscape of cannabinoid use in a more severely affected population and inform future-controlled studies of cannabinoids in headache patients.

Background: Migraine, including episodic migraine (EM) and chronic migraine (CM), is a common neurological disorder that imparts a substantial health burden., Objective: Understand the characteristics and treatment of EM and CM from a population-based perspective., Methods: This retrospective population-based cross-sectional study utilized administrative data from Alberta. Among those with a migraine diagnostic code, CM and EM were identified by an algorithm and through exclusion, respectively; characteristics and migraine medication use were examined with descriptive statistics., Results: From 79,076 adults with a migraine diagnostic code, 12,700 met the criteria for CM and 54,686 were considered to have EM. The majority of migraineurs were female, the most common comorbidity was depression, and individuals with CM had more comorbidities than EM. A larger proportion of individuals with CM versus EM were dispensed acute (80.6%: CM; 63.4%: EM) and preventative (58.0%: CM; 28.9%: EM) migraine medications over 1 year. Among those with a dispensation, individuals with CM had more acute (13.6 ± 32.2 vs. 4.6 ± 10.9 [mean ± standard deviation], 95% confidence interval [CI] 7.7-8.3), and preventative (12.6 ± 43.5 vs. 5.0 ± 12.6, 95% CI 6.9-8.4) migraine medication dispensations than EM, over 1-year. Opioids were commonly used in both groups (proportion of individuals dispensed an opioid over 1-year: 53.1%: CM; 25.7%: EM)., Conclusions: Individuals with EM and CM displayed characteristics and medication use patterns consistent with other reports. Application of this algorithm for CM may be a useful and efficient means of identifying subgroups of migraine using routinely collected health data in Canada.

Background: The aim of this study was to characterize the burden of illness of migraine in Canada. The primary objective was to estimate the annual direct medical resource use and associated costs in migraine patients who failed at least two prophylactic therapies for migraine., Methods: Adults with at least four migraine days per month and who had failed at least two prophylactic migraine therapies were included. Participation in a clinical trial within 12 months of enrollment was the sole exclusionary criterion. Patient demographic and clinical characteristics, migraine-related treatment and medical history, and direct medical resource utilization were collected through a retrospective medical chart review. Data on patient characteristics, lifestyle factors, treatments, medical resource utilization, out-of-pocket expenses, and indirect costs were collected through a cross-sectional patient survey. The patient survey also included validated patient-reported outcome instruments to assess migraine impact on quality of life and work productivity loss., Results: In total, 287 migraine patients were included. The mean time since migraine diagnosis was 14.3 years and patients experienced a mean of 14.1 migraine days per month. The total estimated annual cost of chronic migraine (CM) was $25,669 per patient, while the annual total costs for high-frequency episodic and low-frequency episodic migraine (EM) were estimated to be $24,885 and $15,651, respectively., Conclusion: Migraine is associated with moderate to severe disability. This results in substantial economic burden, directly from healthcare costs such as prescription medications and indirectly through lost work productivity. We also observed that patients with high-frequency EM experience significant burden, similar to that observed for patients with CM.

The Spanish flu spread from September 23, 1918 to 1920. This disease was one of the historical catastrophes in Iran, and a large number of people in Tehran were infected. Evidence also shows that 5000-10000 out of the 250000 infected people died in Tehran over three years. Besides, an increase was detected in the prevalence of other diseases such as pericarditis, orchitis, mastoiditis, meningitis, optic neuritis, paralysis of the palate, mania, cholera, and dysentery. Overall, five percent of the city were destroyed, and the population and economic development were severely damaged. This study aims to evaluate the importance of the history of local medicine in Tehran, the spread of Spanish flu, World War I, and presence of Russian, Ottoman, and British troops in Iran during the flu outbreak. The critical role of Britain in artificial famine, malnutrition, and drug embargo was assessed, as well., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes., Methods: Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7-15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis., Results: We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks., Conclusions: We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.

Malaria is still a global health concern with more than 400,000 death annually. Personal protection using mosquitoes' repellent is an effective prevention strategy, especially in endemic areas. The toxic effects of synthetics repellents and their adverse effects on fabricated goods have made the development of green repellent critical. In this study, ingredients of Zataria multiflora essential oil (ZMEO) were identified using GC-MS analysis. Solid-lipid nanoparticles containing ZMEO (1%) were prepared (SLN-ZMEO) using the high-pressure homogenizer method. The repellent activity of ZMEO and SLN-ZMEO was investigated using Klun and Debboun method and compared together. Besides, their cytotoxicity on a human skin normal cell line (HFFF2) was evaluated. Five major components of ZMEO were carvacrol (27.05%), thymol (26.452%), γ-terpinene (15.144%), o-cymene (13.584%), and α-pinene (9.483%). The SLN-ZMEO showed a spherical shape with a particle size of 134 ± 7 nm. Moreover, their polydispersity index (PDI), zeta potential and entrapment efficiency were determined as 0.24 ± 0.1, - 9.82 ± 0.95 mV and 64.6 ± 3.8%, respectively. Interestingly, the protection time of nanoformulation (93 ± 5 min) was three times longer than that of the non-formulated essential oil (29 ± 2 min). Interestingly, both samples did not show cytotoxicity on HFFF2. Therefore, the prepared nanoformulation can be used as a green and potent repellent., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society for Parasitology 2020.)

Migraine is one of the top 5 most prevalent childhood diseases; however, effective treatment strategies for pediatric migraine are limited. For example, standard adult pharmaceutical therapies are less effective in children and can carry undesirable side effects. To develop more effective treatments, improved knowledge of the biology underlying pediatric migraine is necessary. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions in adults with migraine; however, they have yet to be assessed in children with migraine. Using MRS and GABA-edited MRS, we show that children (7-13 years) with migraine and aura had significantly lower glutamate levels in the visual cortex compared to controls, the opposite to results seen in adults. In addition, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together, this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to pediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in development of more effective treatments.