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Introduction Malaria is an endemic infection in tropical circles. It can be transmitted from mosquitoes bite, but exceptional cases have been attributed to multiorgan transplantation. Case report This is a 34 years-old woman who received a heart transplant for final stage dilated cardiomyopathy. Over the hospitalization, she developed fever, cephalalgia, and tonic-clonic seizures with MRI findings compatible with posterior reversible encephalopathy. A thick blood smear revealed hemoparasitic forms of Plasmodium vivax. Afterward, malaria was also diagnosed in recipients of one kidney and liver of the same organ-donor. First-line treatment with artesunate was prescribed for three days and chloroquine with primaquine thereafter for fourteen days. The patient was discharged and returned to the emergency department five days later, complaining of gastrointestinal symptoms and develop multiorgan failure that led to death. Conclusion We report a case of malaria transmission through heart transplantation. Despite adequate and supervised treatment, it can be related to a fatal outcome. Malaria screening in organ donors should be considered in regions where endemicity can lead to rare cases of transmission by transplantation.

Assessments of physical activity and recommendations to exercise have been a routine part of the evaluation of patients with various headache disorders. There is a great deal of exciting research in the field to support these recommendations. A recent meta-analysis supports aerobic exercise intervention for reduction of migraine frequency (Lemmens et al., J Headache Pain 20:16, 2019), and one trial showed that vigorous aerobic physical activity 3 days per week for 40 min at a time was as effective as preventive treatment with topiramate (Varkey et al., Cephalalgia 31:1428–1438, 2011). Several studies support the use of low-load endurance craniocervical and cervicoscapular exercise for tension-type headache (Cote et al., Eur J Pain 23:1051–1070, 2019). Guidelines now suggest an early return to graduated aerobic exercise training for the amelioration of concussion-related symptoms, including post-traumatic headache (McCrory et al., Br J Sports Med 51:838–847, 2017). The mechanisms by which exercise improves headache symptoms are not fully elucidated. They may include neuroinflammatory, neuromodulatory, cerebrovascular, and psychological effects in migraine, as well as muscle control of cervicoscapular region in tension-type and cervicogenic headache. In reviewing data for various exercise programs, it is important to keep in mind that every prescription for exercise should be individualized to a patient’s level of fitness, should include a combination of aerobic fitness as well as strength exercises as per guidelines for all healthy adults (Piercy et al., JAMA 320:2020–2028, 2018), and should specify intensity, frequency, and duration of exercise that may benefit a specific headache disorder.

Despite migraine being described for thousands of years, the pathophysiology of this disorder is still not completely understood. Migraine is a form of sensory dysfunction, with many manifestations (Pathophysiology and Genetics of Migraine. Headache. p. 88–99; Goadsby et al., Physiol Rev 97(2):553–622, 2017). Migraineurs exhibit photic allodynia and dysfunctional baseline central sensory processing indicating the brain of a migraineur differs from a nonmigraineur even at baseline (Kim et al., Cephalalgia 30(1):53–61, 2010; Vanagaite et al., Cephalalgia 17(7):733–741, 1997). Genetics are known to play a part in migraine as there is a statistically higher incidence of migraine amongst first degree relatives and in identical twins with migraine (Goadsby and Holland, Neurol Clin 37(4):651–671, 2019). Studies examining the potential mode of inheritance have been conflicting, indicating the etiology of migraine likely stems from a complex interaction between genes and the environment (Pathophysiology and Genetics of Migraine. Headache. p. 88–99). There is a consistent correlation of migraine with aura with disorders such as familial hemiplegic migraine illustrating the importance of genetics (Pathophysiology and Genetics of Migraine. Headache. p. 88–99). In addition, environmental triggers such as changes in weather and different food are known to play a significant role in migraine generation. This chapter will review the current knowledge of the pathophysiology of migraine through an examination of the four major phases of a migraine: premonitory, aura, headache, and postdrome.

A 51-year-old man with no past medical history of headache or risk factors for vascular diseases was diagnosed with supraventricular tachycardia (SVT) in 2005. In 2014 SVT attacks were longer and always followed by severe headache attacks. Accompanying symptoms were dizziness, non-rotational vertigo, confusion, episodes of double vision and tinnitus; these symptoms would last one day, followed by severe tiredness for 2 days. Neurologic and cardiologic evaluation as well as extensive diagnostic test between the attacks was normal. Catheter coronarography showed no stenoses but did show spasms in distal left anterior descending artery. A remarkable effect on SVT and headaches was shown after the introducement of diltiazem. The diagnosis cardiac cephalalgia (CC) was established. As our case report is unique, we hope that our observations will help cardiologists and neurologists to better understand and treat patients with CC. CC should be distinguished from migraine, to avoid prescribing triptans and vasoconstrictors.

Introduction: Botulinum neurotoxin type-A (BoNTA) is licensed for the treatment of chronic migraine (CM), but it has been tested off-label as a therapeutic choice in other primary headaches (PHs). We aimed to provide a systematic review and expert opinion on BoNTA use in PHs, beyond CM.Areas covered: After providing an overview on PHs and mechanism of BoNTA action, we report the results of a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of BoNTA therapeutic trials in PHs beyond CM. Studies and results were reviewed and discussed, and levels of evidence were graded. We also collected data on relevant ongoing trials.Expert opinion: Although there are contradictory findings on PHs other than CM, BoNTA may represent a therapeutic option for patients who do not respond to conventional prophylactic treatments. Based on limited available evidence, BoNTA may be considered in refractory tension-type headache, trigeminal autonomic cephalalgias, primary stabbing headache, nummular headache, hypnic headache, and new daily persistent headache, after the primary nature of cephalalgia has been documented and other drugs have failed. Experienced physicians in BoNTA treatment are required to guide the therapeutic protocol for each patient to optimize good and safe outcomes.

Background: COVID-19 has not impacted people or countries uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis in small cohorts, but larger confirmatory data-sets are lacking. Moreover, the global predisposition to experience primary headache disorders might be correlated with variances in COVID-19 mortality rates. Methods: We conducted a meta-analysis of studies of COVID-19 inpatient survival that also reported headache as a COVID-19 symptom. Separately, using a generalized additive model regression (GAM), we analysed data across 171 nations to identify variables which impact COVID-19 mortality rates. We performed similar analyses of seasonal influenza mortality. Prevalence data were extracted from the Global Health Data Exchange. Findings: We meta-analysed 48 studies and observed a significantly higher risk ratio of survival (RR:2·178 [1·882-2·520], p

SummaryIntroductionThe pandemic caused by the new coronavirus (COVID-19) has led to changes in the development of health care activities by health professionals. We analysed whether there is an association between the appearance of “de novo” headache according to the type of mask used, the related factors, as well as the impact of the headache on health professionals.Methodcross-sectional study in a tertiary hospital in Extremadura, Spain. We administered an online questionnaire to healthcare workers during the period of maximum incidence of COVID-19 in our setting.Resultsn=306, 244 women (79.7%), with an average age of 43 years (range 23-65). Of the total, 129 (42.2%) were physicians, 112 (36.6%) nurses and 65 (21.2%) other health workers. 208 (79.7%) used surgical masks and 53 (20.3%) used filtering masks. Of all those surveyed, 158 (51.6%) presented “de novo” headache. The occurrence of headache was independently associated with the use of a filtering mask, OR 2.14 (IC95% 1.07-4.32), being a nurse OR 2.09 (IC95% 1.18-3.72) or another health worker OR 6.94 (IC95% 3.01-16.04) or having a history of asthma OR 0.29 (IC95% 0.09-0.89). Depending on the type of mask used there were differences in headache intensity. And the impact of headache in the subjects who used a filtering mask was worse in the all aspects evaluated.ConclusionsThe appearance of “de novo” headache is associated with the use of filtering masks and is more frequent in certain health care workers, causing a greater occupational, family, personal and social impact.

After traumatic brain injury (TBI), a host of symptoms of varying severity and associated functional impairment may occur. One of the most commonly encountered and challenging to treat are the post-traumatic cephalalgias. Post-traumatic cephalalgia (PTC) or headache is often conceptualized as a single entity as currently classified using the ICHD-3. Yet, the terminology applicable to the major primary, non-traumatic, headache disorders such as migraine, tension headache, and cervicogenic headache are often used to specify the specific type of headache the patients experiences seemingly disparate from the unitary definition of post-traumatic headache adopted by ICHD-3. More complex post-traumatic presentations attributable to brain injury as well as other headache conditions are important to consider as well as other causes such as medication overuse headache and medication induced headache. Treatment of any post-traumatic cephalalgia must be optimized by understanding that there may be more than one headache pain generator, that comorbid traumatic problems may contribute to the pain presentation and that pre-existing conditions could impact both symptom complaint, clinical presentation and recovery. Any treatment for PTC must harmonize with ongoing medical and psychosocial aspects of recovery.

Retropharyngeal abscess caused by tuberculosis (TB) is an unusual life-threatening disease. We present the case of a patient, mainly complaining about dysphagia, cephalalgia, and neck pain. History, examination, and laboratory data were inconclusive. Diagnostic imaging revealed retropharyngeal abscess with atypical characteristics. Aspiration through the pharynx was performed. The aspirated fluid sent for microscopic examination by polymerase chain reaction (PCR) gene probe, revealed Mycobacterium tuberculosis (MTB). Subsequently, the patient was treated with a standard nine-month anti-TB chemotherapy. The combination of fine-needle aspiration and antitubercular agents was successful. The aim of the present study is to inform the importance of early diagnosis with targeted therapy.

RESUMO: Introdução: A cefaleia é uma das queixas somáticas relacionadas a problemas de saúde mais comuns entre crianças e adolescentes. Objetivo: Estimar a prevalência de cefaleia em adolescentes da cidade de São Paulo, Brasil, e fatores associados. Métodos: Trata-se de estudo transversal de base populacional, realizado em 2015, com 539 adolescentes de ambos os sexos, entre 15 e 19 anos de idade. Coletaram-se as informações por inquérito domiciliar, e selecionaram-se os participantes com base em amostragem probabilística. Utilizaram-se na análise frequências, teste χ2 e análise de regressão logística. Adotou-se nível de significância de 5%. Resultados: A prevalência estimada de cefaleia é de 38,2% (intervalo de confiança - IC95% 33,8 - 42,7), de dor de cabeça simples 32,8% (IC95% 28,8 - 37,2) e de enxaqueca 7,8% (IC95% 5,6 - 10,7). Os fatores associados encontrados com cefaleia foram: ser do sexo feminino (razão de chances/odds ratio - OR = 2,2; IC95% 1,4 - 3,4), transtorno mental comum (TMC) (OR = 2,8; IC95% 1,7 - 4,9), problema de visão (OR = 2,6; IC95% 1,6 - 4,2), dor nas costas (OR = 2,2; IC95% 1,3 - 3,5), sinusite (OR = 2,0; IC95% 1,2 - 3,4) e ter escolaridade com ensino fundamental II incompleto (OR = 3,0; IC95% 1,6 - 5,6). Conclusão: A prevalência de cefaleia em adolescentes da cidade de São Paulo em 2015 representou mais de 1/3 (um terço) dessa população. Os principais fatores associados foram sexo, baixa escolaridade e as comorbidades TMC e problema de visão. ABSTRACT: Introduction: Cephalalgia is one of the most common somatic complaints related to health problems in childhood and adolescence. Objective: To measure the cephalalgia prevalence in adolescents from the city of São Paulo, Brazil, and associated factors. Methods: This is a cross-sectional population-based study, carried out in 2015, with 539 adolescents of both sexes, aged between 15 and 19 years. The information was collected in a household survey, and the participants were selected from probabilistic sampling. Frequencies, χ2 test and logistic regression analysis were used in the study, and significance level was 5%. Results: the estimated prevalence of cephalalgia was 38.2% (95%CI 33.8 - 42.7), and 7.8% (95%CI 5.6 - 10.7), migraine. The associated factors for cephalalgia were: female sex (OR = 2.2; 95%CI 1.4 - 3.4), Common Mental Disorder (OR = 2.8; 95%CI 1.7 - 4.9), vision impairment (OR = 2.6; 95%CI 1.6 - 4.2), besides back pain (OR = 2.2; 95%CI 1.3 - 3.5), sinusitis (OR = 2.0; 95%CI 1.2 - 3.4) and incomplete elementary education (OR = 3.0; 95%CI 1.6 - 5.6). Conclusion: The prevalence of headache among adolescents in the city of São Paulo represented more than 1/3 (one third) of this population. The main associated factors were sex, low schooling and the following comorbidities: common mental disorder and vision impairment.

Background Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits. Case presentation In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment. Conclusions The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL.

The avenue of effective migraine therapies blocking calcitonin gene-related peptide (CGRP) transmission is the successful outcome of 35 years of translational research. Developed after short-acting, the small antagonists of the CGRP receptor (the "gepants"), the monoclonal antibodies blocking CGRP or its receptor (CGRP/rec mAbs) have changed the paradigm in migraine treatment. Contrary to the classical acute medications like triptans or nonsteroidal anti-inflammatory drugs (NSAIDs) with a transient effect, they act for long durations exclusively in the peripheral portion of the trigeminovascular system and can thus be assimilated to a durable attack treatment, unlike the classical preventives that chiefly act upstream on the central facets of migraine pathophysiology. Randomized controlled trials (RCT) of eptinezumab, erenumab, fremanezumab and galcanezumab have included collectively several thousands of patients, making them the most extensively studied class of preventive migraine treatments. Their results clearly indicate that CGRP/rec mAbs are significantly superior to placebo and have been comprehensively reviewed by Dodick [Cephalalgia 2019;39(3):445-458]. In this review we will briefly summarize the placebo-subtracted outcomes and number-needed-to-treat (NNT) of these pivotal RCTs and analyze new and post-hoc studies published afterwards focusing on effect size, effect onset and sustainability, response in subgroups of patients, safety and tolerability, and cost-effectiveness. We will also summarize our limited real-world experience with one of the CGRP/rec mAbs. Although methodological differences and lack of direct comparative trials preclude any reliable comparison, the overall impression is that there are only minor differences in efficacy and tolerability profiles between the four monoclonals: the average placebo-subtracted 50% responder rates for reduction in migraine headaches are 21.4% in episodic migraine (NNTs: 4-5), 17.4% in chronic migraine (NNTs: 4-8). Patients with an improvement exceeding 50% are rare, chronic migraineurs with continuous headache are unlikely to be responders and migraine auras are not improved. The effect starts within the first week after administration and is quasi maximal at one month. It is sustained for long time periods and may last for several months after treatment termination. CGRP/rec mAbs are effective even after prior preventive treatment failures and in patients with medication overuse, but the effect size might be smaller. They significantly reduce disability and health care resource utilization. The adverse effect profile of CGRP/rec mAbs is close to that of placebo with few minor exceptions and despite concerns related to the safeguarding role of CGRP in ischemia, no treatment-related vascular adverse events have been reported to date. Putting the CGRP/rec mAbs in perspective with available preventive migraine drug treatments, their major advantage seems not to be chiefly their superior efficacy but their unprecedented efficacy over adverse event ratio. Regarding cost-effectiveness, preliminary pharmaco-economic analyses of erenumab suggest that it is cost-effective for chronic migraine compared to no treatment or to onabotulinumtoxinA, but likely not for episodic migraine unless attack frequency is high, indirect costs are considered and its price is lowered.

A fascinating array of rare headache disorders—Alice in Wonderland syndrome, blip syndrome, cardiac cephalalgia, epicrania fugax, exploding head syndrome, harlequin syndrome, lacrimal headache, ictal epileptic headache, neck–tongue syndrome, and red ear syndrome—are reviewed in this chapter. Appropriate diagnosis and treatment as appropriate can be most reassuring to the patient. There are additional rare headache disorders just waiting to be described by astute clinicians.

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14 years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia - isolated or associated with neurological symptoms - and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment. WHAT THIS PAPER ADDS: Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus. Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.

Cluster headache (CH) is a rare trigeminal cephalalgia that is associated with extremely painful unilateral headache attacks and autonomic symptoms. Attacks may be episodic or chronic and associated with substantial suffering due to excruciating pain and limited treatment options. Frequent cluster headaches cause substantial burden for patients, resulting in reduced productivity caused by disability, as well as direct costs in some European countries. Less is known, however, about direct costs of recurring health care resource utilization (HCRU) in the United States.To characterize HCRU and direct costs associated with CH in the United States from a third-party payer perspective.This retrospective observational study analyzed claims data from the Truven Health Analytics MarketScan Research Databases from 2009-2014. Two cohorts were compared: CH (2 diagnostic CH claims) and controls (nonheadache patients). All patients were enrolled continuously for ± 12 months from date of first CH claim. HCRU and direct costs were examined during 12 months post-index as all-cause and CH-specific. Cost and HCRU differences were compared using propensity score-adjusted bin bootstrapping.CH and control cohorts comprised 6,562 and 143,761 patients (aged ≥ 18 years), respectively. Post-index, 36.9% of CH patients versus 16.2% of controls were admitted to the emergency department (ED), and 14.8% versus 6.1% were hospitalized for any reason, respectively (each P0.001). CH patients had a 2- to 3-fold significantly greater number of all-cause mean claims for outpatient visits (26.5 vs. 12.4 visits), hospital visits (0.2 vs. 0.1 visits), and ED visits (1.0 vs. 0.3 visits) versus controls (all P0.001). The mean number of all-cause visits with reported radiology and laboratory claims was 1.5- to 2.0-fold greater in CH patients versus controls (each P0.001). Mean total direct costs for all-cause claims were more than 2-fold greater in post-index ($16,530) for CH patients versus controls ($7,197, P0.0001). Similarly, mean direct all-cause costs attributable to outpatient, inpatient, and pharmacy claims were significantly (2-fold) greater; radiology and ED claims were 3- to 4-fold greater among CH patients versus controls (all P0.001). However, CH was cited infrequently as a reason for HCRU, indicating that comorbid conditions may substantially increase HCRU in CH patients. The most common reasons for ED admission in CH patients were gastric ulcer with hemorrhage, sub-arachnoid hemorrhage, and headache symptoms. The most common hospital discharge diagnoses for CH patients not observed in top 10 reasons in controls included cerebral artery occlusion/unspecified with cerebral infarction, headache symptoms, syncope/collapse, and diverticulitis.These findings suggest that, from a payer perspective, CH patients incur significantly higher health care costs versus controls. However, these high costs were not exclusively headache-related. Extrapolating our cost findings to estimated U.S. prevalence rates, approximate total direct cost for CH is greater than $2.8 billion/year.Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company.

Celastrus paniculatus belonging to the family Celastraceae generally known as the black oil plant or Malkangani or Jyotishmati. The scrambling through a yellowish corky bark, climbing poly gamodioecious category of shrub requires support to climbs up and distributed almost all over India at the altitude of 2000 m. The seeds are also reported as anxiolytic and anticonvulsant properties, while the root and its bark considered being useful for the treatment of malaria, cancer, and brain-tonic. Plant of Jyotishmati are broadly used in the Ayurvedic system of the medicine to cure many diseases such as; appetizer, aphrodisiac, arthritis, asthma, antipyretic, amenorrhea, anti-inflammatory, acrid, arthralgia, beriberi, cardiotonic, diuretic, diaphoretic, depression, emollient, skin-diseases, paralysis, thermogenic, intellect-promoting, emetic, expectorant, leprosy, leucoderma, cephalalgia, nephropathy, abdominal disorders, sores abortifacient, and treatment of the snake bite. These plants are naturally used in the treatment of vaginal discharge, a sensation of burning, blood purification after delivery, menstruation cycle, and abortion. The seed oil contains steroid alkaloids and bright natural coloring matter, celapanine, celapanigine, celapagine, celastrine, and paniculatine are the important alkaloids. It contains the fatty acid it’s in founding; oleic acid (54.42%), palmitic acid (20.0%), linoleic acid (15.51%), and stearic acid (4.18%). The sesquiterpene alkaloids are derived from a new sesquiterpene (celapanol) which is alternately esterified by acetic, benzoic, nicotinic, and β- furoic acids.

OBJECTIVE To critically appraise the methodological quality of clinical practice guidelines for headache produced over the last two decades, including those covering specific interventions using Traditional Chinese Medicine. METHODS The guidelines on headache disorders were obtained by searching a number of databases, including PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, and Wanfang database, three guideline-related databases [Guideline-International Network, National Guideline Clearinghouse, and Medlive], and the records of organizations that develop guidelines. The publication date was limited to the period from January 1996 to June 2015. The search terms “headache”, “headache disorders”, “cephalalgia”, “migraine”, “tension-type headache”, “practice guideline”, “consensus “, “statement”, “regulation”, and “recommendation” were used in the “MeSH” and “Free-text” fields. The guidelines were independently appraised by four researchers using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS A total of 23 guidelines published between 1998 and 2014 were reviewed. The overall consistency of the four appraisers was good [interclass correlation coefficient 0.84; 95% confidence interval (CI) 0.82–0.86]. The mean (standard deviation) scores for scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence were 52.1 (18.0), 39.5 (17.1), 33.4 (21.0), 49.8 (21.9), 23.8 (19.3), and 24.2 (23.7). Only two guidelines were recommended, 12 were recommended with modification, and nine were not recommended. CONCLUSION Physical Traditional Chinese Medicine therapies were recommended to treat headache. The overall quality of headache guidelines was low in China, but evidence-based guidelines are gradually becoming mainstream. Guideline developers should carefully consider, in particular, three domains: rigor of development, applicability, and editorial independence.

Ethnopharmacological relevance The fruits of Phyllanthus emblica Linn or Emblica officinalis Gaertn (Phyllanthaceae), (FPE) commonly known as Indian gooseberry or Amla, gained immense importance in indigenous traditional medicinal systems, including Ayurveda, for its medicinal and nutritional benefits. It is used to cure several diseases such as common cold, fever, cough, asthma, bronchitis, diabetes, cephalalgia, ophthalmopathy, dyspepsia, colic, flatulence, hyperacidity, peptic ulcer, erysipelas, skin diseases, leprosy, hematogenesis, inflammation, anemia, emaciation, hepatopathy, jaundice, diarrhea, dysentery, hemorrhages, leucorrhea, menorrhagia, cardiac disorders, and premature greying of hair. Aim of the study In the present review, we presented a comprehensive analysis of the ethnopharmacology, bioactive composition, and toxicity of P. emblica to identify the gap between research and the current applications and to help explore the trends and perspectives for future studies. Materials and methods We collected the literature published before April 2021 on the phytochemistry, pharmacology, and toxicity of FPE. Literature in English from scientific databases such as PubMed, ScienceDirect, Wiley, Springer, and Google Scholar, books. These reports were analyzed and summarized to prepare this review. The plant taxonomy was verified by “The Plant List” database ( http://www.theplantlist.org ). Results and conclusion s: FPE have been used as a rich source of vitamin C, minerals, and amino acids. Several bioactive molecules were isolated and identified from FPE such as tannins, flavonoids, saponins, terpenoids, alkaloids, ascorbic acid etc. The in vitro and in vivo pharmacological studies on FPE revealed its antimicrobial, antioxidant, anti-inflammatory, anti-diabetic, anticancer, radioprotective, hepatoprotective, immunomodulatory, hypolipidemic, anti-venom, wound healing, HIV-reverse transcriptase effect. Toxicological studies on fruits indicated the absence of any adverse effect even at a high dose after oral administration. Conclusions Although FPE showed remarkable therapeutic activities against several diseases such as diabetes, cancer, inflammation, hepatitis B virus, and malaria, there were several drawbacks in some previous reports including the lack of information on the drug dose, standards, controls, and mechanism of action of the extract. Further in-depth studies are required to explain the mechanism of action of the extracts to reveal the role of the bioactive compounds in the reported activities.

Background: Deep brain stimulation (DBS) and the proper target for chronic cluster headache (CCH) are still subjects of controversy. Objectives: We present our long-term results of analysis of the target and its structural connectivity. Methods: Fifteen patients with drug-resistant CCH underwent DBS in coordinates 4 mm lateral to the III ventricular wall and 2 mm behind and 5 mm below the intercommissural point. The clinical parameters recorded were the number of weekly attacks, pain intensity, and duration of the headache. Structural connectivity was studied using 3-T MR diffusion tensor imaging (DTI). Results: All of our patients improved from a mean of 39 attacks/week to 2; pain intensity decreased from 9 to 3 out of 10, and the mean cephalalgia duration decreased from 53 to 8 min. The mean stereotactic coordinates of the effective contact location were 6.1 mm lateral to the midcommissural point and 1.2 mm behind and 4.0 mm below the intercommissural point. DTI analysis showed that this target was connected to tracts and nuclei of the posterior mesencephalic tegmentum, specifically the dorsal longitudinal and mamillotegmental fasciculi. Conclusions: Our data showed DBS to be a safe and useful procedure for the treatment of drug-resistant CCH; the rate of improvement was higher than those found in other series. Although these are promising results, larger series targeting those fasciculi with a longer follow-up are needed.

Cardiac cephalalgia is an uncommon symptom occurring in coronary artery disease. It is difficult to identify cardiac cephalalgia and link it to coronary artery disease because these patients present with only a headache and no typical symptoms of angina, such as chest pain, radiating pain, or chest tightness. Currently, the diagnostic value of cardiac cephalalgia in acute myocardial infarction is still under debate. We here report a case of cardiac cephalalgia. An 83-year-old woman with a severe headache lasting 6 h was diagnosed with acute myocardial infarction. ST elevation and severe stenosis of the right coronary artery were observed. Passage of the guide wire and radiocontrast agent increased the intensity of the headache, which disappeared once the right coronary artery was opened. As of one month into follow-up, the headache had not recurred. These observations strongly indicate a close association between cardiac cephalalgia and acute myocardial infarction, and they could help diagnose acute myocardial infarction related to headaches.

Aim. The objective of this study was detecting of neurological pathology among first grade students.Materials and methods. We examined 2507 students (1414 male and 1093 female) in the age from 16 to18 in the process of deep medical examination. We collected neurological complains, neurostatus, analyses of medical documentation. This data was statistically handled.Results. Therefore 80% of students had neurological pathology. The most frequent cases were vegetative-vascular dystonia, vertebrogenic pathology and essential headache.Conclusions. The gained data means the very high level of neurological disease among students, which shows not only importance of rehabilitation activities, but modernization of preventive activities among adolescences.

An herbaceous perennial ornamental plant indigenous to Europe, Asia and mountainous districts of India, cultivated in the United States, and grows in waste places on chalky soils. The abortive properties and the toxicity of its essential oil are known since antiquity; its abortifacient effect has been observed in humans; its leaves and flowers are reported emmenagogue. Pliny said that traveler who has the herb tied about him feel no wearisomeness and cannot be hurt by poisonous medicines, nor by any wild beast. It is described as astringent, deobstruent, anti-inflammatory, diuretic, expels bilious humours, strengthens stomach and liver, and is beneficial in chronic fevers and scorpion bites. Steeped in vinegar it is used as fomentation to head in cephalalgia, to joints in gout and rheumatism, and for painful sprains and bruises. It is also used in hysteria, in spasmodic afflictions like epilepsy, in nervous irritability, depression, and mental exhaustion. The herbage or its juices are used for various types of cancers and indurations of the breast, foot, larynx, liver, sinax, spleen, stomach, testicles, tongue, and uterus, but the oil is a narcotic poison. In Iranian traditional medicine, it is known as an orexigenic (appetite stimulating) herb, and applied topically to abdomen for stomach weakness, swelling and pain, gastric abscess, vomiting, diarrhea and intestinal worms, and used as insect and mosquito repellent. In Uighur traditional medicine, it is used for the treatment of liver disorders. It is the most commonly used herbs for treatment of neonatal jaundice, and is available in China as a decoction. In Korean traditional medicine, it has been used to clear ‘damp heat’ and to treat uteritis, and jaundice. In rural Dominican medical practices, wormwood is used to treat intestinal parasites. In Trinidad and Tobago, it is used for menstrual pain, reproductive issues, and unspecified female complaints. In Central Italy, it is used as antiparasitic and insect repellent, and for tendon inflammation. It was also the main ingredient of a bitter alcoholic drink marketed in Europe as ‘Absinthe’ which was popular in certain artistic circles and reputed to stimulate creativity and possessed exciting, aphrodisiacal and healing properties. A. absinthium is approved for GI disorders use in Europe since Nov. 2005, by the HMPC of the European Medicines Agency.

Cardiac cephalalgia is a migraine-like headache that occurs during episodes of myocardial ischaemia. Clinical characteristics of the headache vary widely but are often severe in intensity, worsen with reduced myocardial perfusion and resolve with reperfusion. It can present along with typical symptoms of angina pectoris, although not always. We present a 64-year-old man with a 6-month history of severe, non-exertional headaches occurring with increasing frequency. A resting ECG showed ST elevation in the inferior leads. His serum troponin I was not elevated. Coronary angiography showed severe stenosis of his right coronary artery, which was successfully stented by percutaneous coronary intervention. He remains headache free at 2-year follow-up.

This article is a Letter to the Editor and does not include an Abstract.

Occipital neuralgia, also known as Arnold’s neuralgia, is a pathology that occurs in 0.1–4.7% of patients with cephalalgia [1]. It is defined by the International Headache Society (IHS) [2] as paroxysmal, shooting or stabbing pain lasting from a few seconds to minutes and starting in the occipital region before radiating within (and often beyond) the distribution of the greater occipital nerve (i.e., Arnold’s nerve, emanating from the C2 and C3 roots), lesser occipital nerve (emanating from the C2 root), or third occipital nerve (from the C3 root). These attacks are sometimes triggered by cold or by cervical movements. Tenderness to palpation of the emergence of the occipital nerve is frequently observed. The neurological examination was normal apart from occasional subjective anomalies (dysesthesia or hypoesthesia affecting a part of the scalp). Between attacks, there is occasionally a persistence of dull headache with variable characteristics (mimicking migraine, tension-type headache, cervical headache, or headache from overuse of analgesics, which are the main differential diagnoses). The syndrome is usually improved by infiltration of the nerve with local anesthetic. Cervicogenic headache (term introduced by Bovim et al. [3]) is precisely defined by the IHS as pain referred from the neck and perceived in one or more regions of the head and/or the face compatible with a cervical spine origin and can be abolished by a block of the cervical spine. But many chronic cervicogenic headaches became occipital neuralgias without efficient treatment and occipital neuralgias are frequently accompanied by tenderness of the neck muscles.

Primary headaches are a common indication for review in neurology clinics. Migraines, tension-type headaches and trigeminal-autonomic cephalalgia (TAC) are the most common primary headache disorders. Migraines can cause significant functional disability and cluster headaches (the commonest TAC) are one of the worst pains known to mankind. Pharmacological treatment has been the standard for both abortive and prophylactic intervention for many years, but there are patients who are refractory to medical therapy and there are others who cannot take such medications because of co-morbidities or cannot tolerate the side effects.

The aim was to evaluate whether headache experts rarely, if ever, investigate spontaneous or provoked migraine/headache attacks. All the 494 Original Articles in five volumes of Cephalalgia (from 2014 to 2018) were screened and classified as dealing with spontaneous or provoked migraine/headache attacks, or other aspects of migraine/headache. Only 4.9% (24/494) of papers reported on studies of spontaneous and provoked migraine/headache attacks. Investigations of the pathophysiology of spontaneous or provoked migraine/headache attacks in humans could result in the development of better drugs for migraine, and to the identifications of biomarkers for use in personalized medicine.

According to the basic theories of traditional Chinese medicine, Gastrodia elata (GE) is clinically utilized for the treatment of cephalalgia and migraine. The gastrodigenin (p–hydroxybenzyl alcohol, HBA), one of the effective components of GE, may pass through the blood–brain barrier (BBB) to exert its pharmacological effects. This study aimed to investigate BBB permeability of HBA via in vitro hCMEC/D3 BBB model and in vivo microdialysis in rats. For the establishment of in vitro BBB model, hCMEC/D3 cells were used to construct the monolayer. The integrity of the monolayer was evaluated by TEER measurements, expression analysis of tight junction proteins (claudin-5, zo-1 and occludin) and apparent permeability coefficients (Papp) of fluorescein disodium. During the 6-day incubation of hCMEC/D3 cells, the values of TEER gradually increased and maintained above 100 Ω·cm2. Besides, the expression levels of claudin-5 and zo-1 in hCMEC/D3 cells increased over time, and tended to be stable, suggesting that integrity of the monolayer has been completely established. Moreover, the Papp of fluorescein disodium was 3.94 × 10−7 cm·s−1 after administration for 180 min, indicating that the monolayer retains the characteristics of BBB and can restrict the diffusion of hydrophilic small-molecule compounds. A sensitive HPLC method was established for HBA detection, and the transport rate of HBA was assessed by a transwell system. HBA crossed the hCMEC/D3 BBB model rapidly, but a plateau was observed when HBA concentrations were relatively similar between the two sides of transwell. Permeability assay revealed that 32.91% of HBA could penetrate the in vitro BBB model after 240 min of administration. In vivo BBB permeability was evaluated by determining the concentrations of HBA in blood and brain simultaneously. Following HBA administration, the samples of microdialysis were collected at 20, 40 and 60 min, and then every 30 min until the procedure ended. Pharmacokinetic parameters of HBA showed that HBA could pass through BBB and reach its maximum concentration at 40 min in blood and brain tissue. Furthermore, AUC0–t and AUC0–inf for the brain–to–blood distribution ratio of HBA were 0.1925 and 0.2083, respectively, indicating that approximately 20% of HBA in blood could pass through the BBB and subsequently transported into the brain. Both in vitro and in vivo experiments confirmed that HBA could penetrate the BBB. In summary, the findings of this study highlight that a promising amount of HBA in blood can pass through the BBB and exerts its pharmacological effects on central nervous system (CNS) diseases.

In the Mediterranean basin, one of the most important agents of myiasis is Oestrus ovis Linnaeus 1758 (Diptera, Oestridae). Herein, we report a rare case of nasal myiasis with a secondary infection complication in a patient from northern Italy who had been visiting Corsica. A healthy, 39-year-old Italian woman spent 2 weeks of vacation in Corsica in June 2018. During her stay, she suddenly felt a foreign body inside her nose, followed by cough, pain, burning at the pharyngeal level, cephalalgia, and nasal congestion with secretions from the nostrils. The clinical examination showed a hyperemic and irritated mucosa and endoscopic examination of the patient’s nose and right maxillary sinus revealed three tiny mobile larvae, morphologically and molecular identified as L1 instar larvae of Oestrus ovis. The patient’s infestation was probably imported from Corsica, as Mediterranean islands are ideal geographical areas for the development of O. ovis, and the timing of infestation match with the period of O. ovis larviposition. Although rhinomyiasis is rare, it should be considered in people returning from abroad presenting with an acute-onset and foreign body sensation in the nose.

Objectives To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases. Materials & methods Retrospective chart review of neurological patients receiving IVIg treatment between July 13, 2017, and August 14, 2017. Patients with MS receiving natalizumab in the same setting were observed as a reference group. Results Patients with headache after IVIg infusion (n = 22 infusions) showed a reduced heart rate (by 6.0 ± 8.5 beats per minute [bpm]), but no significant difference in blood pressure. Patients without headache after IVIg infusion (n = 69 infusions) showed a higher systolic blood pressure increase and a stronger reduction in the heart rate (by 5.7 ± 8.6 bpm), compared to patients with headache after IVIg infusion. The infusion rate was significantly slower and age significantly lower in patients developing headache after IVIg infusion. Body temperature was unchanged in both groups. Binary logistic regression analysis revealed that blood pressure at baseline and age significantly influence the occurrence of cephalalgia. In reference, patients receiving natalizumab (ie, shorter infusions/smaller infusion volume), systolic blood pressure, and heart rate decreased, while body temperature increased. Here, one patient developed headache. Conclusions Intravenous immunoglobulin-associated headache is not associated with an increased blood pressure after infusion but with a reduced heart rate, a slower infusion rate, female sex and seems to be influenced by baseline systolic blood pressure and age. A reaction to immunoglobulin aggregates, stabilizers, or vasoactive mediators are possible explanations. The absence of an association with body temperature does not suggest a systemic immune response as a cause for headache.

In the recent years, migraine has been widely studied by scholars from all over the world. This study aimed to use scientometric methods to identify research frontiers and development trends in the field of migraine research. We used the Web of Science (WoS) core collection database to collect articles and reviews related to migraine published from 2010 to 2019 on March 25, 2020. VOSviewer, CiteSpace, and Excel were used for the scientometric analysis. A total of 6,357 publications (including 5,203 articles and 1,154 reviews) were identified. The United States published the most publications (n=2,151, 33.84%). Albert Einstein College of Medicine contributed the most publications (n=220, 3.46%). Cephalalgia was found to be the core journal with the most publications (n=766, impact factor 2019 =4.868) as well as the most co-citations (n=35,535). Lipton RB authored the most publications (n=159, 2.50%), while Silberstein SD received the most co-citations (n=4,215). The critical topics were causes and pathophysiological mechanisms, epidemiological characteristics, diagnostic criteria, treatment and prevention drugs, and migraine-related genes. Through the use of scientometric methods, this article has mapped the knowledge landscape of migraine research over the past decade. By showing the overall status of the field, it provides a useful reference for future research.

Purpose of review Management of headache disorders is not part of most craniomaxillofacial surgery practices; however there are certain indications for surgical management of headaches by the craniomaxillofacial surgeon. Recent findings Migraine headaches are the most amenable to surgical management and while the exact mechanism of migraine is unknown, a central or peripheral trigger such as compressive neuropathy of trigeminal nerve branches leading to neurogenic inflammation has been suggested. The primary management for episodic migraine headache should be lifestyle modification and medication, whereas for chronic migraine (>15 headache days/month) use of medication and botulinum neurotoxin is effective, whereas some patients may choose to explore surgical options. Trigger site decompression for chronic migraine surgically relieves anatomic impingement at various sites and has been shown to reduce by at least 50% the frequency, intensity, and duration of headaches in over 85% and elimination of headaches in almost 60%. Trigger points may also lead to exacerbation of cluster headaches and treatment with botulinum neurotoxin may reduce attacks. Summary Trigger site decompression is an effective treatment for chronic migraine, as are botulinum neurotoxin injections in reducing attacks in cluster headaches. The craniomaxillofacial surgeon is uniquely qualified to treat these primary headache disorders.

This article reports the case of a 32-year-old female patient who presented with severe spasmodically occurring retrobulbar pain, headaches and light sensitivity. The neurological examination confirmed cephalalgia but no evidence of other neurological symptoms was found. Ophthalmoscopy revealed yellowish patchy lightened spots in the middle periphery. Fluorescein angiography (FLA) and indocyanine green angiography (ICGA) revealed findings typical for acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Hypofluorescent areas visible using ICGA in the early and late phases showed corresponding hypoperfused areas by optical coherence tomography angiography (OCT-A). To the best of our knowledge this is the first description of these findings in OCT-A.