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Background: Approximately 5-10% of epileptic patients do not respond to antiepileptic drugs. Adenosine has an inhibitory effect on the nervous system and its metabolism is prevented as a side effect of allopurinol, a xanthine oxidase inhibitor. The current study evaluates the efficacy of allopurinol in intractable epilepsy.Methods: In this double-blind case-control clinical trial, of the 38 epileptics with intractable seizures, 18 received 300 mg allopurinol daily and 20 received a placebo as adjuvant treatment to their previous antiepileptic drugs. The patients were first examined two weeks after initiation of the treatment and then monthly for a total of six months, during which they were evaluated for seizure control and possible side effects.Result: Of the 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizures over the entire six-month trial. A seizure reduction of 30% observed in 66% of the patients, 50% in 55%, and 60% in 44% of the cases in the allopurinol group was achieved after two months and persisted throughout the study. Furthermore, a significant difference in seizure duration was found between the two groups in month four of the trial. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness; however, only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one had nausea. In addition, no significant hematological or hepatic changes were found during the trial in either group.Conclusions: The results suggest that allopurinol is a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolic pathways and the specific use of allopurinol should be further investigated for the treatment of refractory epilepsy.

Defining the patient outcome and decision making about allocation of our limited fund and technology for comatose patients depends on our knowledge about frequency and outcome of various coma etiologies. We determined the various coma causes frequency and one-month outcome of non traumatic coma. . In addition the co existence of the primary neurologic signs with the one-month outcome of non traumatic coma was defined."nMethods and Materials: Our study is based on 130 comatose patients in a one-year study in Sina Hospital that consisted of 80 non traumatic and 50 traumatic patients."nResults: 74% of the cases were men and 26% were women. The most common etiology of coma was trauma (38.5%). The other common etiologies were cerebro¬vascular diseases (25.4%), cancer (10%) and hypoxia-ischemia (8.5%). The most common cause of coma in men was trauma (46.9%) while the vascular diseases were the most common etiology of coma in women (41.2%).In under 40 year patients trauma was the cause of coma in 57.5% of cases in respect to 28% in above 40 cases. On the other hand, vascular diseases and malignancies were the etiology of coma in 15% of under 40 year patients and 46.5% of above 40 year patients. Among traumatic etiologies of coma, subdural hematoma was the most frequent (40%). In our research none of patients who did not have one of pupillary, oculocephalic or motor reflexes in the 3rd and 7th day of the onset of coma had acceptable outcome after one month. With consideration of pupillary, corneal, oculocephalic and motor reflexes in combination, loss of at least two of them in the 3rd and 7th day accompanied with no acceptable outcome. On the other hand the presence of three or more reflexes in the 3rd and 7th day of coma was a good prognostic factor, with 80% and 88.9% chance of acceptable recovery respectively."nConclusion: According of the study, the best time for prediction of outcome in a comatose patient, is the third or seventh the day after the onset of coma. Also relay on combination of brain stem reflexes, gives us more acceptable result.

Migraine is a highly prevalent disorder with an enormous burden on societies. Different types of medications are used for controlling both acute attacks and prevention. This article reviews some non-pharmacological recommendations aiming to manage migraine disorder better and prevent headache attacks. Different triggers of migraine headache attacks, including environmental factors, sleep pattern changes, diet, physical activity, stress and anxiety, some medications, and hormonal changes, are discussed. It is advised that they be identified and managed. Patients should learn the skills to cope with the trigger factors that are difficult to avoid. In addition, weight control, management of migraine comorbidities, lifestyle modification, behavioural treatment and biofeedback, patient education, using headache diaries, and improving patients’ knowledge about the disease are recommended to be parts of migraine management. In addition, using neuromodulation techniques, dietary supplements such as riboflavin, coenzyme Q10 and magnesium, and acupuncture can be helpful. Non-pharmacological approaches should be considered in migraine management. Furthermore, the combination of pharmacological and non-pharmacological approaches is more effective than using each separately.

Abstract Saphenous nerve, a pure sensory nerve, may compromise as a result or complication of a surgical procedure or secondary to trauma or insidiously. We present a male patient with low back pain concomitant with pain in medial portion of left thigh in addition to pain and numbness in medial part of leg and inferior part of patella after a strenuous activity. Preliminary diagnosis suggested that the patient had radiculopathy but electrodiagnostic tests revealed the absence of left saphenous response both in medial leg and infrapatellar region, while normal findings were recorded from right side. Needle electromyography in L4 innervated muscles were normal. The patient had saphenous nerve entrapment in left thigh. Two months later symptoms relieved with conservative therapy.

Abstract Background Primary intracerebral hemorrhage (ICH) is one of the common vascular insults with a relatively high rate of mortality. The aim of the current study was to determine the mortality rate and to evaluate the influence of various factors on the mortality of patients with intracerebral hemorrhage (ICH). Demographic characteristics along with clinical features and neuroimaging information on 122 patients with primary ICH admitted to Sina Hospital between 1999–2002 were assessed by multivariate analysis. Results Of 122 patients diagnosed with intracerebral hemorrhage, 70 were men and 52 were women. Sixtynine percent of subjects were between 60 to 80 years of age. A history of hypertension was the primary cause in 67.2% of participants and it was found more frequent compared to other cardiovascular risk factors such as a history of ischemic heart disease (17.2%), diabetes mellitus (18%) and cigarette smoking (13.1%). The overall mortality rate among ICH patients admitted to the hospital was 46.7%. About one third of the deaths occurred within the first two days after brain injury. Factor independently associated with in-hospital mortality were Glasgow Coma Scale (GCS) score (≤ 8), diabetes mellitus disease, volume of hematoma and and intraventricular hematoma. Conclusion Higher rate of mortality were observed during the first two weeks of hospitalization following ICH. Neuroimaging features along with GCS score can help the clinicians in developing their prognosis.

Introduction: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB., Clinical Findings: We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision., Diagnosis: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients., Conclusion: NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella., (© 2024. The Author(s).)

Migraine, a complex disorder, is characterized by recurrent headache episodes. The production of melatonin in the pineal gland, which is crucial for controlling circadian rhythms and sleep-wake cycles, is altered in various conditions, including neurological disorders such as migraine. Recent studies underscore the significance of serum melatonin levels in patients with chronic and episodic migraine, the focus of this study. This case‒control study, conducted from September 2017 to June 2020 in Tehran, Iran, selected potential participants aged 18-65 years from a headache clinic at Sina Hospital (affiliated with Tehran University of Medical Sciences). Both episodic migraine and chronic migraine were diagnosed following the diagnostic criteria in the International Classification of Headache Disorders' third edition. Melatonin levels were measured according to the instructions of the ELISA kits. There were significant differences in the frequency of headache days and the duration of abortive medication usage between the two groups (P value < 0.001). Besides, analysis revealed significantly lower serum melatonin levels in patients with episodic ((80.45-45.06) 72.83) and chronic migraine ((154.34-63.34) 70.38, P value < 0.001) than in healthy controls (281.25-160.86) 280). Although no considerable differences were found between episodic and chronic migraine patients, the current study demonstrated that serum melatonin levels were substantially greater in healthy controls than in patients with migraine., (© 2024. The Author(s).)

Importance: Pediatric migraine substantially impacts quality of life and academic performance among children and adolescents. Understanding the efficacy and safety of pharmacological interventions for migraine prophylaxis in this population is crucial for developing effective treatment strategies., Objective: To conduct a comprehensive network meta-analysis to evaluate the efficacy and safety associated with pharmacological treatments for pediatric migraine prophylaxis among pediatric patients with a migraine diagnosis and assess interventions involving various oral pharmacological interventions compared with each other and placebo., Data Sources: PubMed, Embase, and SCOPUS were searched for publications up to September 2023. Search terms and indexing were chosen to encompass relevant studies, focusing on randomized clinical trials in pediatric migraine prophylaxis., Study Selection: Inclusion criteria targeted randomized clinical trials involving pediatric patients with migraine. Studies were selected based on their examination of oral pharmacological interventions. The search yielded an initial 9162 citations., Data Extraction and Synthesis: Data extraction adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Five investigators independently extracted study data into a spreadsheet in duplicate. Study-level estimates were calculated, employing a random-effects model for primary and secondary outcomes due to identified heterogeneity. Data analysis was conducted from December 2023 to March 2024., Main Outcomes and Measures: The primary outcome was migraine frequency (number of attacks per month). Secondary outcomes included a 50% or greater responder rate, headache duration, headache intensity, and disability (assessed by pediatrics migraine-specific disability tool). Adverse events were also evaluated., Results: The analysis incorporated 45 trials with 3771 participants. Compared with placebo, pregabalin (ratio of means [RoM], 0.38; 95% CI, 0.18-0.79) and topiramate with vitamin D3 (RoM, 0.44; 95% CI, 0.30-0.65) were associated with reduction in migraine frequency. Flunarizine (RoM, 0.46; 95% CI, 0.26-0.81), levetiracetam (RoM, 0.47; 95% CI, 0.30-0.72), riboflavin (RoM, 0.50; 95% CI, 0.32-0.77), cinnarizine (RoM, 0.64; 95% CI, 0.46-0.88), topiramate (RoM, 0.70; 95% CI, 0.55-0.89), and amitriptyline (RoM, 0.73; 95% CI, 0.54-0.97) were also associated with reduction in migraine frequency, but these findings were drawn from individual studies. For the 50% or greater responder rate, flunarizine and α-lipoic acid (risk ratio [RR], 8.73; 95% CI, 2.44-31.20), flunarizine (RR, 4.00; 95% CI, 1.38-11.55), pregabalin (RR, 1.88; 95% CI, 1.13-3.14), and cinnarizine (RR, 1.46; 95% CI, 1.04-2.05) were associated with significantly greater effectiveness than placebo. Compared with placebo, propranolol and cinnarizine (RoM, 0.45; 95% CI, 0.28-0.72), pregabalin (RoM, 0.57; 95% CI, 0.33-0.96), valproate (RoM, 0.60; 95% CI, 0.49-0.72), levetiracetam (RoM, 0.62; 95% CI, 0.50-0.77), and cinnarizine (RoM, 0.64; 95% CI, 0.54-0.76) were significantly associated with reduction in headache intensity. However, no treatments were associated with significant improvements in quality of life or reduction of the duration of migraine attacks. Adverse events were higher with amitriptyline (RR, 3.81; 95% CI, 1.41-10.32), topiramate (RR, 4.34; 95% CI, 1.60-11.75), and valproate (RR, 5.93; 95% CI, 1.93-18.23) compared with placebo., Conclusions and Relevance: In this network meta-analysis of randomized clinical trials, topiramate and pregabalin were associated with reduction in headache frequency and intensity. Although there were also other drugs that showed statistically significant results (flunarizine, riboflavin, amitriptyline, and cinnarizine), more studies were required for a robust conclusion. None of the drugs were associated with improved quality of life or attack duration, underscoring the need for further research to develop more comprehensive treatment strategies and explore the potential of combination therapies, especially those involving vitamins. Future studies should focus on validating these findings and expanding the treatment landscape for pediatric migraine management.

Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from Abbvie and Teva. Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer. Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs. Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of Journal of Headache Pain, and associate editor of Brain. Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an associate editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the editorial board for Journal of Headache Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society. Eric Liebler declares consulting fees from ElecroCore, Inc. Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant. Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler. Esme Ekizoğlu declares honoraria from Allergan-AbbVie. David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer. Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain. Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva. Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita Pharm. Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma. Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, International Headache Society (IHS), National Institute for Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB. Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris. Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis. Mi Ji Lee declares consulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu. Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan. Daniele Martinelli declares honoraria from AbbVie and Lundbeck. Teshamae S. Monteith has the following disclosures over the past three years: clinical trial site principal investigator for studies sponsored by Abbvie, Eli Lilly, Ipsen and Rehaler, participation in advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. Dr Monteith has provided unpaid service on the board of directors for the International Headache Society (2021-2023) and currently on the executive board for the Florida Society of Neurology. Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva. Aynur Özge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan. Mario Peres accepted honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. MP is president of ABRACES. Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva. Todd J. Schwedt declares grants/contracts with American Heart Association, Amgen, Henry Jackson Foundation, National Headache Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, United States Department f Defense, American Migraine Foundation and Mayo Clinic. Consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix. He declares royalties from UpToDate and stock options from Aural. Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly. Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma. Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea. Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent. Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen. Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from AbbVie, Eli Lilly, Dompé, Ipsen, Lundbeck, Pfizer, Medscape, Teva. All remaining authors report no disclosures or conflicts of interest

Background: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications., Methods: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group., Results: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained., Conclusion: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from TEVA.Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer.Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs.Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of the Journal of Headache and Pain, and associate editor of Brain.Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an Associate Editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the Editorial Board for the Journal of Headache and Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society.Eric Liebler declares consulting fees from ElecroCore, Inc.Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant.Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler.Esme Ekizoğlu declares honoraria from Allergan‐AbbVie.David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer.Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain.Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva.Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita pharm.Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma.Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, IHS, National Institute of Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB.Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris.Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis.Mi Ji Lee declares onsulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu.Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan.Daniele Martinelli declares honoraria from AbbVie and Lundbeck.Teshamae S. Monteith has the following disclosures over the past 3 years: clinical trial site principal investigator for studies sponsored by Eli Lilly and AbbVie (all paid to the institution), participation in an advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. TSM has provided unpaid service on the board of directors for the International Headache Society (2021–2023) and currently on the executive board for the Florida Society of Neurology.Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva.Aynur Ozge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan.Mario Peres accepted honoraria for lectures, presentations, speakers bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. Mario Peres is president of ABRACES.Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva.Todd J. Schwedt declares grants/contracts with AHA, Amgen, Henry Jackson Foundation, NIH, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, US Dept. of Defense, AMF, NHF and Mayo Clinic with consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix.Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly.Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma.Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea.Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent.Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen.Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, Medscape.All remaining authors report no disclosures or conflicts of interest.

Background: We recently found headache disorders to be highly prevalent among children (aged 6-11 years) and adolescents (aged 12-17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study., Methods: In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country's diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains., Results: The analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores reflected these measures of burden., Conclusions: Headache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran., (© 2024. The Author(s).)

Migraine headaches are the most prevalent disabling primary headaches, affecting individuals at an active age. Dietary interventions are considered low-cost and practical approaches to migraine prophylaxis. Hence, the present study aimed to assess the association between adherence to the Healthy Eating Index 2015 (HEI-2015) and migraine headaches. The present case-control study was conducted on 476 newly diagnosed adults with migraine headaches, based on the International Classification of Headache Disorders 3rd edition (ICHDIII criteria(, and 512 healthy controls. Participants' dietary intakes were collected using a validated, 168-item semi-quantitative food frequency questionnaire (FFQ). The association between HEI-2015 and migraine headaches was assessed using logistic regression models. Although the trend was not statistically significant, being in the 4th quantile of the HEI-2015 was associated with about 50% lower odds of migraine headaches in both primary (adjusted for age and gender) (odds ratios (OR): 0.51, 95% confidence intervals (CI): 0.33, 0.78) and fully adjusted models (additionally adjusted for body mass index (BMI) and total calories) (adjusted OR: 0.50, 95%CI: 0.32, 0.77). Intriguingly, the odds of migraine headaches were significantly higher in those in the last quantile of "Total Fruits," which is equal to more than 237 g per 1000 kcal (aOR: 2.96, 95%CI: 1.99, 4.41) and "Whole Fruits," which is equal to more than 233 g per 1000 kcal (aOR: 2.90, 95%CI: 1.94, 4.31). Similarly, higher intakes of "Dairy," which is equal to more than 138 g per 1000 kcal (aOR: 2.66, 95%CI: 1.71, 4.14), and "Total Protein Foods," which is equal to more than 259 g per 1000 kcal (aOR: 2.41, 95%CI: 1.58, 3.70), were associated with higher odds of migraine headaches. The current study revealed an indirect association between HEI-2015 and its components, including "Greens and Beans," "Whole Grains," "Refined Grains," and "Added Sugars" and lower odds of migraine headaches., Competing Interests: D.F., M.N., S.RJ., M.T., Z.Gh., A.H., P.R., Z.T., P.Sh., H.A., A.K., and F.Kh. declare that they have no competing interests., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Purpose: To our knowledge, no studies have evaluated the association between dietary glycemic index (GI) and glycemic load (GL) with migraine-related clinical symptoms., Methods: This cross-sectional study was conducted among 266 women with episodic migraine. The migraine disability assessment (MIDAS) was used to evaluate migraine-related disability in the recent three months. Visual analogue scales (VAS) were also employed to examine migraine-related pains. Glycemic index and glycemic load indices were calculated using the nutritional information obtained from the food frequency questionnaire., Results: The study participants had a mean age of 34.32 ± 7.86 years. It was observed that individuals in the quartile 4 of GI and GL reported significantly higher consumption of calories, carbohydrates, proteins, and fats ( P  < 0.05). In the unadjusted models, those in the quartile 4 of GI and GL had significantly increased odds of experiencing severe pain (based on VAS score) (OR = 2.09, 95% CI = 1.37-2.70, P  < 0.001 for dietary GI, and OR = 1.75, 95% CI = 1.16-2.79, P  = 0.005 for dietary GL). Additionally, compared to participants in the quartile 1 of GI and GL, those in the quartile 4 of GI and GL were more likely to suffer from severe disability ( P  < 0.05)., Conclusion: We found a significant positive correlation between the consumption of foods with higher GI and GL and the clinical conditions related to migraine disease. However, due to the cross-sectional nature of the study, it is not possible to establish a cause-and-effect relationship for the observed results.

Background: Neck pain is a common complaint among migraineurs possibly due to the anatomic connections between cervical and trigeminal afferents in the trigeminocervical complex (TCC). Manual therapy (MT) is used in the management of headache disorders, with demonstrable neurophysiological effects. The blink reflex (BR) is one method of analyzing neurophysiological effects in headache patients. The purpose of this study was to investigate the effect of upper cervical spine MT on BR in subjects with migraine and neck pain., Methods & Materials: Twenty subjects were assigned to a medication plus MT (MedMT) group ( n  = 10) and medication plus sham MT (sham MT) group ( n  = 10). After random assignment, all patients underwent testing for the BR (R1, R2, R2c responses). Then, subjects in group MedMT and group sham MT received either 4 sessions of MT or sham MT to the upper cervical spine. After completion of the intervention, BR testing was repeated., Results: There were no significant differences in both side R1 latency between group MT and group sham MT ( P  > 0.050). For both sides, R2 latencies were significantly prolonged in MedMT group compared with sham MT group ( P  < 0.050). Subjects in MedMT group showed significant prolongation in right and left R2c latency compared with sham MT group ( P  < 0.050)., Discussion: The present study demonstrated that upper cervical MT affected trigeminal nociceptive neurotransmission in subjects with migraine and neck pain as reflected by changes in the BR. The increase in BR late response latencies of BR indicates an inhibitory effect of upper cervical spine MT on the TCC in these subjects. Trial Registration: The trial design was registered at the Iranian Registry of Clinical Trials (IRCT ID: IRCT20160621028567N2, url: https://www.irct.ir/) before the first patient was enrolled.

Background: Mucolipidosis type IV (MLIV) is a rare, progressive lysosomal storage disorder characterized by severe intellectual disability, delayed motor milestones and ophthalmologic abnormalities. MLIV is an autosomal recessive disease caused by mutations in the MCOLN1 gene, encoding mucolipin-1 which is responsible for maintaining lysosomal function., Objectives and Methods: Here, we report a family of four Iranian siblings with cognitive decline, progressive visual and pyramidal disturbances, and abnormal movements manifested by severe oromandibular dystonia and parkinsonism. MRI scans of the brain demonstrated signal abnormalities in the white matter and thinning of the corpus callosum., Results and Conclusions: Whole-exome sequencing identified a novel homozygous variant, c.362C > T:p. Thr121Met in the MCOLN1 gene consistent with a diagnosis of MLIV. The presentation of MLIV may overlap with a variety of other neurological diseases, and genetic analysis is an important strategy to clarify the diagnosis. This is an important point that clinicians should be familiar with. The novel variant c.362C > T:p. Thr121Met herein described may be related to a comparatively older age at onset. Our study also expands the clinical spectrum of MLIV associated with the MCOLN1 variants and introduces a novel likely pathogenic variant for testing in MLIV cases that remain unresolved.

Objective: Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries., Methods: We analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria., Results: Among patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD., Conclusions: Other primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Since the beginning of the COVID-19 pandemic, a number of COVID-related neurological manifestations have been reported. We aimed to categorize the features of hospitalized COVID-19 patients who experienced neurological symptoms., Methods: In this descriptive, cross-sectional study, we enrolled all patients hospitalized with COVID-19 who experienced neurological symptoms in two hospitals in Tehran. Diagnosis of COVID-19 was established by PCR tests or computed tomography of the chest combined with COVID-19 clinical findings. The clinical characteristics, laboratory data, and imaging findings from 365 patients were analyzed., Results: The average patient age was 59.2 ± 16.7 years and included 213 males and 152 females. The most prevalent neurological symptoms were headache (56.2%), impaired consciousness (55%), and dizziness (20.5%). During hospitalization, most of the patients did not require mechanical ventilation (81.9%). The percentage of patients with end-organ damage was 9% and mortality was 15%. Regression analysis on the neurological symptoms indicated that the mortality rate of patients with headaches was 84% lower than for the other neurological symptoms. Hyperglycemia was significantly related with end-organ damage and mortality (p = 0.029, p = 0.08, respectively). New vascular lesions were evident on brain MRIs of 9 patients and brain CTs of 16 patients., Conclusion: Among the neurological symptoms of patients with COVID-19, headache appeared to indicate a protective factor against development of end-organ damage as well as mortality., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Tension-Type Headache (TTH) is regarded as the third most prevalent disorder worldwide, prompting children to seek medical attention. Our objective is to investigate the prevalence of TTH among students aged 6 to 18 years in various geographical regions of Iran, while also assessing the impact of headaches on their quality of life., Methods: Employing a cross-sectional survey, we have carefully distributed self-completed structured questionnaires to students in 121 meticulously selected schools throughout the country, ensuring the representation of its diverse population., Results: Among the 2,958 potential participants, we have included a total of 2031 individuals in our study. This comprises 57.3% children and 42.7% adolescents, with 50.02% being males and 49.97% females. Specifically, we have examined 950 subjects with TTH and 1,081 individuals without any form of headache. TTH was diagnosed in 32.1% of the participants. Notably, we have observed a significant difference in the average age between the TTH subjects and those without headaches. Participants without headaches were more likely to be enrolled in primary schools, while those diagnosed with TTH predominantly attended high schools. We found no significant relationship between urban-rural areas or different geographic regions and the prevalence of TTH or its subtypes. Phonophobia was commonly associated with TTHs. Lastly, the mean quality-of-life score was highest for individuals without headaches, followed by those with low frequency episodic TTH, high frequency episodic TTH, and chronic TTHs. There was also a significant relation between headache severity and quality of life scores., Conclusion: The significant prevalence of TTH in children and adolescents and its adverse impact on the daily activities of individuals underscore the utmost importance of accurate diagnosis and efficient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Togha, Jafari, Salami, Kamali, Mirzaee Godarzee, Mirzaee Godarzee and Bavarnegin.)

Background: Headache is the most frequent neurological adverse event following SARS-CoV-2 vaccines. We investigated the frequency, characteristics, and factors associated with post-vaccination headaches, including their occurrence and prolongation (≥ 48 h)., Methods: In this observational cross-sectional cohort study, retrospective data collected between April 2021-March 2022 were analyzed. Univariate and multivariate logistic regressions were used to evaluate the effect of clinicodemographic factors on the odds of post-vaccination headache occurrence and prolongation., Results: Of 2,500 people who were randomly sent the questionnaire, 1822 (mean age: 34.49 ± 11.09, female: 71.5%) were included. Headache prevalence following the first (V 1 ), second (V 2 ), and third (V 3 ) dose was 36.5, 23.3, and 21.7%, respectively ( p  < 0.001). Post-vaccination headaches were mainly tension-type (46.5%), followed by migraine-like (36.1%). Headaches were mainly bilateral (69.7%), pressing (54.3%), moderate (51.0%), and analgesic-responsive (63.0%). They mainly initiated 10 h [4.0, 24.0] after vaccination and lasted 24 h [4.0, 48.0]. After adjusting for age and sex, primary headaches (V 1 : aOR: 1.32 [95%CI: 1.08, 1.62], V 2 : 1.64 [1.15, 2.35]), post-COVID-19 headaches (V 2 : 2.02 [1.26, 3.31], V 3 : 2.83 [1.17, 7.47]), headaches following the previous dose (V 1 for V 2 : 30.52 [19.29, 50.15], V 1 for V 3 : 3.78 [1.80, 7.96], V 2 for V 3 : 12.41 [4.73, 35.88]), vector vaccines (V 1 : 3.88 [3.07, 4.92], V 2 : 2.44 [1.70, 3.52], V 3 : 4.34 [1.78, 12.29]), and post-vaccination fever (V 1 : 4.72 [3.79, 5.90], V 2 : 6.85 [4.68, 10.10], V 3 : 9.74 [4.56, 22.10]) increased the odds of post-vaccination headaches. Furthermore, while primary headaches (V 1 : 0.63 [0.44, 0.90]) and post-COVID-19 headaches (V 1 : 0.01 [0.00, 0.05]) reduced the odds of prolonged post-vaccination headaches, psychiatric disorders (V 1 : 2.58 [1.05, 6.45]), headaches lasting ≥48 h following the previous dose (V 1 for V 2 : 3.10 [1.08, 10.31]), and migraine-like headaches at the same dose (V 3 : 5.39 [1.15, 32.47]) increased this odds., Conclusion: Patients with primary headaches, post-COVID-19 headaches, or headaches following the previous dose, as well as vector-vaccine receivers and those with post-vaccination fever, were at increased risk of post-SARS-CoV-2-vaccination headaches. Primary headaches and post-COVID-19 headaches reduced the odds of prolonged post-vaccination headaches. However, longer-lasting headaches following the previous dose, migraine-like headaches at the same dose, and psychiatric disorders increased this odd., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jameie, Togha, Azizmohammad Looha, Jafari, Yazdan Panah, Hemmati and Nasergivehchi.)