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

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

Management of medication overuse headache.

Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked. Treatment includes education and prevention; withdrawal programs; pharmacological prophylaxis; multidisciplinary therapies with behavioral and noninvasive neuromodulation options; and scheduled, frequent follow-up to prevent relapses. The advent of anti-CGRP therapy monoclonal antibodies may provide an alternative to more extensive programs for less complex patients. This review also provides guidance for which patients may benefit most from coordinated integrated programs.

[Brain iron deposition increases in the bilateral substantia nigra of patients with medication-overuse headache: a quantitative susceptibility mapping analysis].

OBJECTIVE: To investigate iron accumulation level over the whole brain and explore the possible neuromechanism of medication-overuse headache (MOH) using quantitative susceptibility mapping (QSM). METHODS: Thirty-seven MOH patients and 27 normal control subjects were enrolled in the study for examinations with both a multiecho gradient echo magnetic resonance (MR) sequence and brain high resolution structural imaging. A voxel-based analysis was performed to detect the brain regions with altered iron deposition, and the quantitative susceptibility mapping values of the positive brain regions were extracted. Correlation analysis was performed between the susceptibility values and the clinical variables of the patients. RESULTS: In patients with MOH, increased susceptibility values were found mainly in the bilateral substantia nigra (SN) (MNI coordinate: 8, -18, -14; -6, -16, -14) as compared with the normal control subjects (P < 0.001), but these alterations in iron deposition were not significantly correlated with the clinical variables of the patients (P > 0.05). The susceptibility value in the left SN had an area under curve (AUC) of 0.734, and at the cut-off value of 0.077, its diagnostic sensitivity was 72.97% and its specificity was 70.37% for distinguishing MOH from normal controls; The susceptibility value in the right SN had an AUC of 0.699 with a diagnostic sensitivity of 72.97% and a specificity of 62.96% at the cut-off value of 0.084. CONCLUSION: Increased iron deposition occurs in the bilateral SN of MOH patients, which provides a new insight into the mechanism of mesocorticolimbic dopamine system dysfunction in MOH. QSM technique can be used as a non-invasive means for quantitative analysis of brain iron deposition in migraine neuroimaging.

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

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

Sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache.

OBJECTIVE: The present study aimed to compare sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache (MOH). METHODS: Consecutive patients with newly diagnosed chronic migraine (CM) with and without MOH based on the Third Edition of International Classification of Headache Disorders (ICHD-3) were enrolled prospectively from the headache clinic of a tertiary medical center. Demographics and clinical profiles were collected by using a questionnaire, which included current use of tobacco, alcohol, and caffeinated beverages, the Leeds Dependence Questionnaire (LDQ), the Severity of Dependence Scale (SDS), the Headache Impact Test-6 (HIT-6), and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 1419 CM patients (1135F/284 M, mean age 41.7 ± 13.9 years) were recruited, including 799 with MOH (640F/159 M, mean age 42.5 ± 13.2 years) (56.3%). Smoking was associated with an increased risk for MOH in men (odds ratio [OR] = 3.60 [95% confidence interval = 1.73-7.50], p = 0.001), but not in women (OR = 1.34 [0.88-2.04], p = 0.171) (p = 0.021 for interaction). Hypnotic use ≥ 3 days/week was a risk factor for MOH (OR = 2.55 [95% confidence interval = 2.00-3.24], p < 0.001), regardless of sex. By using receiver operating characteristics (ROC) curves, the cutoff scores of the LDQ for MOH were determined at 7 for women and 6 for men, and those for the SDS were 5 and 4, respectively (area under curve all ≥ 0.83). Among patients with MOH, the male sex was associated with a shorter latency between migraine onset and CM onset (12.9 ± 11.1 vs. 15.4 ± 11.5 years, p = 0.008), despite less average headache intensity (6.7 ± 1.9 vs. 7.2 ± 1.9, p = 0.005), functional impacts (HIT-6: 63.4 ± 8.3 vs. 65.1 ± 8.0, p = 0.009), and sleep disturbances (PSQI: 10.9 ± 4.4 vs. 12.2 ± 4.3, p = 0.001). CONCLUSIONS: The current study identified an association between smoking and MOH in men, as well as sex-specific cutoffs of the LDQ and the SDS, for MOH. MOH was characterized by a shorter latency between migraine onset and CM onset in men and a more severe phenotype in women. Sex should be considered as an important factor in the evaluation of MOH.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Tratamiento con bloqueo esfenopalatino de la cefalea refractaria por trombosis del seno cavernoso / Treatment with sphenopalatine blockade against refractory headache due to thrombosis of the cavernous sinus

Introducción: Entre las cefaleas secundarias se encuentra la atribuida a flebotrombosis cerebral producida por trombosis séptica del seno cavernoso. El ganglio esfenopalatino interviene en la génesis y mantenimiento de cefaleas unilaterales; pues envía conexiones a la cavidad nasofaríngea y meninges, así desempeña una función importante en la modulación neuronal; el bloqueo de dicho ganglio es un método fácil, seguro, económico y efectivo de tratamiento del dolor irruptivo de algunos tipos de cefalea. Objetivo: Presentar los resultados del bloqueo GEFP en el tratamiento de la cefalea grave refractaria secundaria a trombosis séptica del seno cavernoso. Presentación de caso: Paciente de 71 años de edad, al que se realizó de forma exitosa bloqueo transnasal del ganglio esfenopalatino, para tratamiento de cefalea grave refractaria secundaria a trombosis séptica del seno cavernoso, consiguiéndose analgesia efectiva con disminución progresiva de la cefalea y control total de la misma a las 72 h de tratamiento. Conclusiones: El bloqueo podría constituir una opción en la terapéutica de este tipo de cefalea(AU)

Introduction: Among secondary headaches, one is attributed to cerebral phlebothrombosis produced by septic thrombosis of the cavernous sinus. The sphenopalatine ganglion (SPG) is involved in the genesis and maintenance of unilateral headaches, since it sends connections to the nasopharyngeal cavity and meninges, playing thus an important role in neuronal modulation; therefore; the blockade of this ganglion is an easy, safe, economic and effective method for treating breakthrough pain in some types of headache. Objective: To present the results of SPG blockade in the treatment of refractory severe headache produced by septic thrombosis of the cavernous sinus. Case presentation: A 71-year-old male patient is presented, who was successfully performed a transnasal SPG blockade, as a treatment for refractory severe headache caused by septic thrombosis of the cavernous sinus. Effective analgesia is achieved, together with progressive decrease of headache until it was totally controlled at 72 hours. Conclusions: Blockade was an option in the therapy of this type of headache(AU)

Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.

Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.

Interictal plasma endothelin-1 levels do not change in individuals with episodic and chronic migraine.

BACKGROUND: Individuals with migraine present ictal elevation of endothelin-1 levels. Migraine can be subclassified into episodic migraine and chronic migraine. Apart from the inconsistent reports on interictal endothelin-1 levels, most studies did not distinguish between episodic migraine and chronic migraine. METHODS: We measured plasma endothelin-1 levels in participants with episodic migraine (n = 87), with chronic migraine (n = 88), and controls (n = 50). RESULTS: Interictal endothelin-1 levels were not significantly different among participants with episodic migraine, those with chronic migraine, and controls (pg/ml, median and interquartile range, 10.19 [7.76-13.69] vs. 9.25 [6.91-10.73] vs. 9.46 [7.00-14.19], p = 0.131). After excluding participants with fibromyalgia (n = 50) and medication-overuse headache (n = 21), endothelin-1 levels were still similar among groups (10.51 [7.96-14.10] vs. 9.24 [6.96-10.81] vs. 9.46 [7.00-14.19], p = 0.230). Endothelin-1 levels did not significantly differ among participants with migraine with aura, those with migraine without aura, and controls (9.36 [4.26-13.35] vs. 9.50 [7.23-13.02] vs. 9.46 [7.00-14.19], p = 0.975). There was no significant association of endothelin-1 with headache intensity (mild, 8.99 [8.99-8.99] vs. moderate, 8.71 [6.85-12.15] vs. severe, 9.55 [7.23-13.13], p = 0.517) or headache frequency per month (exponential and 95% confidence interval, 0.709 [0.296-1.698], p = 0.440) in participants with episodic migraine and chronic migraine. CONCLUSIONS: Interictal plasma endothelin-1 level is an unlikely marker for episodic migraine and chronic migraine.

Medication overuse headache and awareness / Cefaleia por abuso de medicação e conscientização

ABSTRACT Background: Medication overuse headache (MOH) is the worsening of an underlying headache due to the overuse of its acute treatment. Unintentionally, healthcare professionals may contribute to this condition. Health professionals play an important role in preventing this increasingly frequent and difficult-to-treat condition. Objective: To investigate MOH awareness among physicians with headache through a survey conducted among medical doctors on our university campus. Methods: This was an observational cross-sectional study about MOH awareness. The total number of medical doctors working in the Dokuz Eylül University Health Campus was provided by the administrative unit. A total of 18 questions were prepared and administered on a voluntary basis to obtain information about MOH awareness. Results: A total of 312 medical doctors were surveyed, including 198 (63.5%) from internal medical sciences, 81 (26%) from surgical medical sciences, and 33 (10.5%) from basic medical sciences. Half of the physicians in our sample were unaware of MOH. Our results showed that awareness of MOH, was quite low even among medical doctors. Conclusions: MOH causes both labor and financial losses to countries and impairs the quality of life of patients. Preventing excessive use of medications by raising awareness among doctors is an important step to prevent the development of MOH.

RESUMO Antecedentes: A cefaleia por uso excessivo de medicamentos (CEM) é o agravamento de uma cefaleia subjacente devido ao uso excessivo do seu tratamento agudo. Involuntariamente, os profissionais de saúde podem contribuir para essa condição. Os profissionais de saúde desempenham um papel importante na prevenção dessa condição cada vez mais frequente e de difícil tratamento. Objetivo: Investigar a conscientização da CEM entre médicos com dor de cabeça por meio de uma pesquisa realizada entre médicos em nosso campus universitário. Métodos: Este foi um estudo transversal observacional sobre a consciência da CEM. O número total de médicos que trabalham no Campus de Saúde da Universidade Dokuz Eylül foi fornecido pela unidade administrativa. Um total de 18 questões foram preparadas e aplicadas de forma voluntária para obter informações sobre a conscientização da CEM. Resultados: Um total de 312 médicos foram pesquisados, incluindo 198 (63,5%) das ciências médicas internas, 81 (26%) das ciências médicas cirúrgicas e 33 (10,5%) das ciências médicas básicas. Metade dos médicos de nossa amostra desconhecia a CEM. Nossos resultados mostraram que o conhecimento sobre a CEM era bastante baixo, mesmo entre os médicos. Conclusões: A CEM causa perdas laborais e financeiras aos países e prejudica a qualidade de vida dos pacientes. Prevenir o uso excessivo de medicamentos por meio da conscientização dos médicos é um passo importante para prevenir o desenvolvimento da CEM.

Evaluation of structural changes in orbitofrontal cortex in relation to medication overuse in migraine patients: a diffusion tensor imaging study / Avaliação das mudanças estruturais no córtex orbitofrontal em relação ao uso excessivo de medicamentos em pacientes com migrânea: um estudo de imagem por tensor de difusão

Abstract Background: Migraine is a prevalent neurological disease that leads to severe headaches. Moreover, it is the commonest among the primary headaches that cause medication overuse headache (MOH). The orbitofrontal cortex (OFC) is one of the structures most associated with medication overuse. Objective: To determine microstructural changes in the OFC among migraine patients who developed MOH, through the diffusion tensor imaging (DTI) technique. Methods: Fifty-eight patients who had been diagnosed with migraine based on the Classification of Headache Disorders (ICHD-III-B) were included in the study. Patients were sub-classified into two groups, with and without MOH, based on the MOH criteria of ICHD-III-B. DTI was applied to each patient. The OFC fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values of the two groups were compared. Results: The mean age of all the patients was 35.98±7.92 years (range: 18-65), and 84.5% (n=49) of them were female. The two groups, with MOH (n=25) and without (n=33), were alike in terms of age, gender, family history, migraine with or without aura and duration of illness. It was found that there was a significant difference in FA values of the left OFC between the two groups (0.32±0.01 versus 0.29±0.01; p=0.04). Conclusions: An association was found between MOH and changes to OFC microstructure. Determination of neuropathology and factors associated with medication overuse among migraine patients is crucial in terms of identifying the at-risk patient population and improving proper treatment strategies specific to these patients.

RESUMO Introdução: A migrânea é uma doença neurológica prevalente que causa fortes dores de cabeça. Além disso, é a mais comum entre as cefaleias primárias que causam cefaleia por uso excessivo de medicamentos (CUEM). O córtex orbitofrontal (OF) é uma das estruturas mais associadas ao uso excessivo de medicamentos. Objetivo: Determinar alterações microestruturais no córtex OF em pacientes com migrânea que desenvolveram CUEM, por meio da técnica de imagem por tensor de difusão (ITD). Métodos: Cinquenta e oito pacientes com diagnóstico de migrânea, com base na Classificação das Cefaleias (ICHD-III-B), foram incluídos no estudo. Os pacientes foram subclassificados em dois grupos, com e sem CUEM, com base nos critérios de CUEM da ICHD-III-B. A ITD foi aplicada a cada paciente. Os valores de anisotropia fracionada OFC (AF) e coeficiente de difusão aparente (CDA) dos dois grupos foram comparados. Resultados: A média de idade de todos os pacientes foi de 35,98±7,92 anos (variação: 18‒65), sendo 84,5% (n=49) do sexo feminino. Os dois grupos, com CUEM (n=25) e sem (n=33), são semelhantes em termos de idade, sexo, história familiar, migrânea com ou sem aura e duração da doença. Verificou-se que houve diferença significativa nos valores de AF do córtex OF esquerdo entre os dois grupos (0,32±0,01 versus 0,29±0,01; p=0,04). Conclusões: Foi encontrada associação entre o CUEM e as alterações na microestrutura do córtex OF. A determinação da neuropatologia e dos fatores associados ao uso excessivo de medicamentos entre pacientes com migrânea é crucial para identificar a população de pacientes em risco e melhorar as estratégias de tratamento adequadas específicas para esses pacientes.

Selective targeting of peripheral cannabinoid receptors prevents behavioral symptoms and sensitization of trigeminal neurons in mouse models of migraine and medication overuse headache.

ABSTRACT: Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and although cannabinoids seem beneficial in alleviating migraine symptoms, central nervous system side effects limit their widespread use. We developed peripherally restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable central nervous system side effects or tolerance development. Here, we determined PRCB effectiveness in alleviating hypersensitivity symptoms in mouse models of migraine and medication overuse headache. Long-term glyceryl trinitrate (GTN, 10 mg/kg) administration led to increased sensitivity to mechanical stimuli and increased expression of phosphorylated protein kinase A, neuronal nitric oxide synthase, and transient receptor potential ankyrin 1 proteins in trigeminal ganglia. Peripherally restricted cannabinoid pretreatment, but not posttreatment, prevented behavioral and biochemical correlates of GTN-induced sensitization. Low pH-activated and allyl isothiocyanate-activated currents in acutely isolated trigeminal neurons were reversibly attenuated by PRCB application. Long-term GTN treatment significantly enhanced these currents. Long-term sumatriptan treatment also led to the development of allodynia to mechanical and cold stimuli that was slowly reversible after sumatriptan discontinuation. Subsequent challenge with a previously ineffective low-dose GTN (0.1-0.3 mg/kg) revealed latent behavioral sensitization and increased expression of phosphorylated protein kinase A, neuronal nitric oxide synthase, and transient receptor potential ankyrin 1 proteins in trigeminal ganglia. Peripherally restricted cannabinoid pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, long-term PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and medication overuse headache.

Secondary stabbing headache associated with intracranial tumors, aneurysms, and arteriovenous malformation: An alarming warning sign.

BACKGROUND: Stabbing headache (SH) is considered as a pure primary headache, but according to a few clinical observations it could also be secondary. Over the past decades, we have been observing the complaint of SH in patients with intracranial vascular and neoplastic lesions. OBJECTIVE: To describe a series of patients with intracranial lesions who experienced SH. METHODS: This is a cross-sectional, retrospective study of 34 patients with intracranial lesions associated with SH, admitted at Hospital das Clínicas, Federal University of Pernambuco, Brazil. RESULTS: In this series of 34 patients [29 women, 44 ± 12 years (mean ± SD)] with secondary SH, the causes were intracranial neoplasms (n = 31), cerebral aneurysms (n = 2), or arteriovenous malformation (n = 1). Pituitary tumor (n = 18), meningioma (n = 6), and vestibular schwannomas (n = 4) were the most prevalent types of intracranial neoplasms. All these lesions had intimate contact with the dura mater, including an oligodendroglioma, the only intra-axial tumor in the series. A characteristic in the secondary SH is the crescendo pattern (12/34, 35%), progressing from infrequent attacks to recurrent crises occurring several times a day. The SH lasted from 5 days to 60 months (15 ± 18 months, mean ± SD) until the correct diagnosis [16/34 (47%) of the patients ≤6 months]. The SH was triggered by the movement of the head (5/34, 15%) or Valsalva maneuver (1/34). After surgery, suppression of the SH was observed. In a few of the patients to whom dexamethasone was prescribed, the SH subsided within a few days. CONCLUSION: This study was able to identify clinical red flags associated with intracranial lesions and secondary SH, for example, recent onset of SH, exclusively unilateral (ipsilateral) at the same location, crescendo pattern, triggered by head movements, or Valsalva maneuver.

Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation.

OBJECTIVE: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved. BACKGROUND: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need. METHODS: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months. RESULTS: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients). CONCLUSIONS: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.

Update on headache and brain tumors.

Headache is one of the leading symptoms often associated with brain tumours. Secondary headaches attributed to intracranial neoplasias have been included in subchapter 7.4 of the third edition of the International Classification of Headache Disorders (ICHD-3). According to ICHD-3, the headache may be attributed to a brain tumour if it has developed in close temporal relation with the development of the neoplasia, has significantly worsened in parallel with the worsening of the tumour, and/or has significantly improved following the successful treatment of the neoplasia. Brain tumour headache was traditionally thought to display some specific clinical characteristics, including worsening in the morning and/or when lying down, being aggravated by Valsalva-like manoeuvres and accompanied by nausea and/or vomiting; however, the studies performed after the advent of modern neurodiagnostic techniques have pointed out that the "classic" brain tumour headache is uncommon, particularly at the time of clinical presentation. Therefore, it becomes critical to seek some specific factors associated with the presence of an intracranial mass (the so-called "red flags") that can guide the physician to establish an accurate diagnosis.

Impulsivity prevalence in migraine patients without and with medication overuse / Prevalência de impulsividade em pacientes com enxaqueca sem e com abuso de medicação

ABSTRACT Background: Migraine is one of the most common disorders in neurological clinical practice and is part of the group of primary headaches. It often affects individuals in the age group of 25-55 years, when people are at their peak of economic productivity. Many patients ultimately overuse analgesics. Overuse is defined by the use of analgesics for at least 15 times a month - within a minimal three-month period. Impulsivity and migraine cause losses in the lives of individuals suffering from them, as they can compromise these individuals' social, emotional, and professional spheres. Regarding the professional sphere, it results in economic losses compared with the overall population. Objective: To investigate the presence of impulsive behavior in patients with migraine and with medication-overuse migraine. Methods: Cross-sectional study on 210 female and male patients; 140 were diagnosed with migraine according to criteria of the International Classification of Headache Disorders and were subdivided into two groups (70 patients each). One of these groups was composed of medication-overuse patients; the control group was composed of non-migraine patients (70 patients). All patients were evaluated with the Barratt Impulsivity Scale (BIS-11). Results: The group of migraine patients accounted for the highest impulsivity level, followed by the control group and, finally, by the medication-overuse group. However, these differences did not attain statistical significance. Conclusions: It was not possible to establish a clear connection between migraine and impulsive behavior. Association was higher among migraineurs without medication overuse.

RESUMO Introdução: A enxaqueca é uma das condições mais comuns na prática clínica neurológica, enquadrando-se no grupo das cefaleias primárias. Sua prevalência é maior na faixa etária de 25 a 55 anos, coincidindo com o pico da produtividade econômica. Muitos pacientes recorrem ao uso abusivo de analgésicos. O uso excessivo desses medicamentos é definido pela sua utilização por pelo menos 15 vezes ao mês, por um período de no mínimo três meses. A impulsividade e a enxaqueca causam prejuízos na vida dos indivíduos afetados, podendo comprometer os âmbitos social, emocional e profissional, resultando em um prejuízo monetário a esse grupo, em relação à população em geral. Objetivo: Investigar a presença de comportamento impulsivo em pacientes com enxaqueca com abuso de analgésico. Métodos: Estudo de corte transversal com 210 pacientes, homens e mulheres, sendo 140 com diagnóstico de enxaqueca segundo os critérios da Classificação Internacional das Cefaleias (IHCD-3), subdivididos em dois grupos de 70 pacientes cada, um composto por pacientes em uso excessivo de medicamentos, e um grupo controle composto por indivíduos sem enxaqueca. Todos os pacientes foram avaliados com a Escala de Impulsividade de Barratt - BIS 11. Resultados: O grupo com enxaqueca apresentou maior impulsividade, seguido do grupo controle e, por fim, o grupo com enxaqueca com abuso de medicamentos. No entanto, essas diferenças não atingiram significância estatística. Conclusão: Não foi possível encontrar relação direta entre a enxaqueca e comportamentos impulsivos. No entanto, esta relação foi maior entre os pacientes com enxaqueca sem abuso de analgésico.

Comparison of translabyrinthine and retrosigmoid approach for treating vestibular schwannoma: A meta-analysis.

BACKGROUND: To date, the literature directly comparing the translabyrinthine approach and retrosigmoid approach in the operation of patients with vestibular schwannoma was limited. We aimed to evaluate postoperative complications between translabyrinthine approach and retrosigmoid approach for treating vestibular schwannoma patients. MATERIAL AND METHOD: Potential publications were selected from PubMed, Web of Science and Cochrane Library. Gray relevant studies were manually searched. We set the searching time spanning from the creation date of electronic engines to February 2020. STATA version 12.0 was exerted to process the pooled data. RESULTS: A total of 9 literature included in the study, involving 2429 patients, hails from the Germany, USA, Canada, Italy, and France. Of these 2429 patients with vestibular schwannoma, there were 1628 cases from the translabyrinthine approach group versus 801 cases from the retrosigmoid approach group. The results demonstrated that the translabyrinthine approach group was associated with a lower rate of tinnitus (OR = 2.687; 95 %CI, 1.167-6.191; P = 0.02) and cranial nerve deficit (OR = 2.946; 95 %CI, 1.562-5.557; P = 0.001). And the translabyrinthine approach group was associated with a higher total resection rate (OR = 0.246; 95 %CI (0.071-0.848); P = 0.026). However, no statistic differences were found in the incidence of the near total (OR = 0.751; P = 0.351), subtotal resection (OR = 3.664; P = 0.109), postoperative facial nerve dysfunctions (OR, 0.763; P = 0.626), postoperative meningitis (OR = 2.7; P = 0.279), cerebrospinal fluid leak (OR = 1.225; P = 0.777), postoperative headache (OR = 1.412; P = 0.339), ophthalmic complications (OR = 0.87; P = 0.59), and vascular complications (OR = 2.501; P = 0.139). CONCLUSION: Based on current evidence, the translabyrinthine approach was associated with a higher rate of total resection and a lower rate of the tinnitus and cranial nerve deficit. But the risk of cranial nerve deficit was clearly affected by the preoperative status. And a translabyrintine approach could imply a complete sensorineural hearing loss, which contribute to the lower rate of postoperative tinnitus. Consequently, more evidence-based researches are needed to supplement this opinion.