Search

The article provides data on the prevalence of migraine. It is shown that migraine patients are characterized by the variability of the incidence, duration and intensity of migraine attacks, range of leading clinical manifestations, as well as the pre­sence of precipitating factors specific for each patient. This work presents a literature review, which describes some pathogenetic aspects of migraine. In this case, the authors define the direct correlation between the incidence of headaches and hormonal changes, the age of patients. It was found that gender differences, hormonal disorders are the important factors for the initiation of migraine attacks. The article presents the data of numerous clinical and experimental studies, which showed that high levels of estrogen are correlated with a higher pain tolerance. The work pays much attention to the problem of comorbidity of migraine, presents clinical case of migraine complicated by cerebral infarction with atypical localization of ischemic focus.

В огляді розглядаються питання діагностики й лікування мігрені й цефалгії напруження. Лікування обох видів цефалгій включає абортивну й превентивну терапію.

Headache is one of the most common pathological conditions worldwide, taking into account that 45 % of the adult population has ever reported severe or disabling cephalgia. This interdisciplinary problem often requires participation of many specialists to perform comprehensive differential diagnosis and to choose the effective management. The article investigates one of the causes of the headache such as infections due to persistent viruses. The article presents a detailed clinical case of recurrent episodes of severe disabling headache in an immunocompetent female, which were accompanied by genital rash. Performed laboratory survey is discussed. Methods and efficacy of therapeutic approach during exacerbation episodes and long-term follow-up are described. The article presents international classification of primary and secondary causes of headache disorders according to the International Headache Society (2013). The spectrum of etiological causes of headache, which should be included into differential diagnosis is discussed. Attention is given to differentiation of headache as a presentation of infectious diseases, both intracranial and systemic. Considering the presented clinical case of recurrent episodes of severe headache associated with signs of genital rash, etiology of herpes simplex virus 1 + 2 is suggested. According to clinicians’ opinion, Mollaret meningitis was diagnosed in the discussed case. The article presents historical background of this diagnosis, pathogenic features of this disorder, diagnostic criteria of Mollaret meningitis, its relation to the group of benign recurrent aseptic meningitis, as well as outline of other reasons of benign meningitis. Recommended management of Mollaret meningitis and its efficacy are provided in the study. Differential diagnosis of recurrent episodes of headache should include a long list of causes and often requires collaboration of different specialists. The combination of recurrent pain of any localization, such as cephalalgia with neurologic or somatic pathology, includes herpes simplex virus 1 + 2 infection in the clinical and laboratory differential diagnosis. When establishing the diagnosis of recurrent aseptic meningitis, such as Mollaret meningitis, first line etiotropic drugs are derivatives of acyclovir unless another cause of serous meningitis is confirmed. The use of acyclovir derivatives with recurrent aseptic meningitis, including Mollaret meningitis, can be justified on the basis of clinical signs in cases when exact etiotropic confirmation is complicated. This therapy should be performed as a long-term suppressive chemotherapy, duration and efficacy of which should be established during further clinical evaluation, considering absence of headache relapses and other clinical presentations.

We describe the case of a 5-month-old girl who presented to the emergency department with left-sided periorbital edema and erythema. During the assessment, she was observed to suffer repeated hyper-acute episodes of screaming associated with left-sided hemifacial flushing, lacrimation and rhinorrhea. This child was diagnosed with probable short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), one of the trigeminal autonomic cephalalgias. We believe that this is the youngest probable case of SUNCT for which there is photographic and video evidence. Int J Clin Pediatr. 2021;10(2-3):49-52 doi: https://doi.org/10.14740/ijcp433

Background Clerodendrum serratum Linn commonly known as Bharangi in India has wide applications in the Ayurveda and Siddha system of medicine which has been attributed to the treatment of various diseases like asthma, cough, fever, rheumatism, and cephalalgia ophthalmia. Squalene has nutritional, medicinal, and pharmaceutical health benefits, hence possess antioxidant and cytoprotective effects. Method The study presents the GC-MS analysis of phytoconstituents present in the Clerodendrum serratum roots and further estimation of one of the constituents, i.e., squalene which is ought to be present in the roots as per mass spectral data obtained. Squalene was determined from the ethanolic extract of C. serratum roots using GC-FID without derivatization. Results Four major constituents, i.e., squalene, methyl palmitate, hexadecenoic acid, and stigmasterol were detected by GC-MS. Squalene from the extract was eluted at 17.5min which was confirmed with the standard squalene peak eluted at the same retention time. The linearity range chosen was 5–30ug/mL, and the method was found to be pretty linear (R=0.995), accurate with satisfactory repeatability. Hence, the phytochemical compounds were detected by GC-MS and the squalene was determined and validated according to the ICH guidelines. Conclusion Thus, the green gas chromatographic method can be used for quantification and qualification of active constituents in the roots of ethanolic extract of C. serratum. In addition, the presence of metabolite squalene by the GC-FID method was developed for the extract which is simple, fast, and environmentally friendly.

The article presents a clinical case of comorbid pathology – development of migraine against the background of systemic mastocytosis. The classification and clinical manifestations of systemic mastocytosis, a rare blood disease, are given. This clinical case illustrates an example of excessive mast cell degranulation (with the release of proinflammatory and vasodilating agents as a result of mast cell pathology). In this regard, in addition to the pathogen-specific therapy for systemic mastocytosis (including prevention of mast cell degranulation), it seems important to describe the effectiveness and the possibility of prescribing preventive and emergency therapy for migraine against the background of the underlying hematological disease – systemic mastocytosis. Treatment of cephalalgia in patients with mastocytosis is a complex clinical task, in the solution of which it is necessary to take into account serious limitations in prescription of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.

Background: Headache is one of the most common causes of emergency care and migraines are the most common primary headache in this regard. Objective: The aim of this research study was to assess the incidence of medical consultations due to headache, along with demographic characteristics and treatments pertaining to cephalalgia that were offered to patients cared for in supplemental healthcare emergency rooms. Methods: In 2017, a total of 11,105 consultations took place, and 4,865 (43.8%) of them were complaints relating to headache. 407 records of patients with headache were randomly selected and assessed. Demographic, clinical and therapeutic data were collected using a structured form. Results: The cause of headache was diagnosed as migraine in 60.0% of the patient records. Patients were mostly female (75.2%), with an average age of 33.9 ± 13.7 years. Patient management consisted of administering dipyrone in 62.4% of cases, antiemetics in 66.9%, corticosteroids in 58.9%, opioids in 24.3% and NSAIDs in 13.5%. Use of opioids was associated with a diagnosis of migraine (OR 2.4; CI 1.4-3.9; p = 0.001). Patients who received opioids were kept under observation for longer periods of time (OR 3.4; CI 2.1-5.4; p < 0.001) and exhibited a higher rate of use of antiemetics (OR 11.0; CI 4.7-25.9; p < 0.001), compared with patients who did not receive opioids. Conclusion: Dipyrone and antiemetics were administered to most of the patients. Opioids were used for a significant proportion of these individuals, despite the diagnosis of migraine, a condition for which their use is discouraged. RESUMO Introdução: Cefaleia é uma das causas mais frequentes de atendimentos de emergência, sendo que a migrânea é a cefaleia primária mais comum nesse contexto. Objetivo: Avaliar a frequência de atendimentos por cefaleias, bem como as características demográficas e o tratamento oferecido aos pacientes atendidos em Pronto Atendimento da Saúde Suplementar. Métodos: No ano de 2017 foram realizados 11.105 atendimentos, sendo 4.865 (43,8%) por queixa de cefaleia. Foram selecionados randomicamente a analisados 407 prontuários de pacientes com cefaleia. Os dados demográficos, clínicos e terapêuticos foram coletados através de formulário estruturado. Resultados: A causa da cefaleia foi diagnosticada como migrânea em 60,0% dos prontuários. Os pacientes eram em sua maioria do sexo feminino (74,9%), com média de idade de 33,9±13,7 anos. O manejo dos pacientes constitui-se na administração de dipirona em 62,4%, antiemético 66,9%; corticóide 58,9%, opióide 24,3% e, por fim, AINE foi utilizado em 13,5% dos casos. O uso de opióide foi associado ao diagnóstico de migrânea (OR 2,4; CI 1,4-3,9; p=0,001). Pacientes que receberam opióide também tiveram maior tempo de permanência (OR 3,4; IC 2,1-5,4; p

Background Migraine and trigemino-autonomic cephalalgia attacks are associated with an increase of α-calcitonin-gene related peptide levels in the ipsilateral jugular vein. It is however unknown whether trigeminal pain stimulation in healthy subjects without headache disorders also induces increase of calcitonin-gene related peptide levels. Findings We measured α-calcitonin-gene related peptide levels in eight healthy subjects after subcutaneous injection of capsaicin in the forehead and in the mandibular region and after injection of sodium chloride in the forehead. We observed a significant increase of α-calcitonin-gene related peptide level only after injection of capsaicin in the forehead (i.e. first trigeminal branch). We also observed trigemino-autonomic activation (lacrimation, rhinorrhea etc.) only after injection of capsaicin in the forehead. Conclusion Increase of α-calcitonin-gene related peptide levels do not only occur in primary headache attacks but also after experimental trigeminal pain of the first branch. This finding suggests that α-calcitonin-gene related peptide elevation is, at least an additional, unspecific effect of first trigeminal branch stimulation following pain activation and not a specific mechanism of idiopathic headache disorders.

Background Migraine is the second-leading cause of disability worldwide. It is often characterized by attacks of severe, mostly unilateral, pulsating headache associated with symptoms such as photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. Acupuncture therapy has been used worldwide for the treatment of migraine. However, no visual bibliometric analysis has been conducted on the effects of acupuncture on migraine over the past 20 years. Therefore, this study aimed to explore the current status and trends on the use of acupuncture in the treatment of migraine from 2000 to 2020. Purpose The objective of this study is to identify the current status and emerging trends of the global use of acupuncture on migraine from 2000 to 2020 using CiteSpace and VOSviewer. Methods Web of Science databases were searched for publications related to acupuncture therapy for treating migraine between 2000 and 2020. CiteSpace and VOSviewer were used to analyze the number of publications per year, countries, institutions, authors, journals, references, and keywords. Results A total of 572 publications were included in the final analysis. The total number of publications has continued to increase with some fluctuations over the past 20 years. The most productive country and institution in this field were the USA, and Chengdu University of Traditional Chinese Medicine, respectively. The most active and cited authors were Liang FR and Linde K, respectively. Cephalalgia was the most productive, cited, and co-cited journal. The Linde K (2005) had the highest co-citation, citation number and centrality. The keywords "migraine" ranked first in frequency. The common type of migraine (tension-type headache), research method (randomized controlled trial, multicenter, double-blind), acupuncture's role (prophylactic, quality of life, pain), and evaluation (meta-analysis, systematic review) were the hotspots and frontier trends of acupuncture therapy on migraine between 2000 and 2020. Conclusion The present study examined the research-related trend in acupuncture therapy on migraine using bibliometric methods and identified the statement and research frontiers over the past two decades. This may help researchers to identify potential hotspots and new directions for future research in this field.

Aim Headache attributed to temporomandibular disorders and myalgia are two diagnoses included in the diagnostic criteria for temporomandibular disorders (DC/TMD). However, it is not clear if these two diagnoses are different clinical entities given their similar presentation and way in which they are diagnosed, when the myalgia is within the temporalis muscle. The purpose of this retrospective study was to assess the overlap between headache attributed to temporomandibular disorders and myalgia of the temporalis muscle. Methods The charts of 671 patients seeking treatment at the Section of Orofacial Pain and Jaw Function, Aarhus University, Denmark, between January 2015 and February 2020 were screened for a diagnosis of headache attributed to temporomandibular disorders, myalgia of the temporalis muscle, or both. Results A total of 89 patients fulfilled the DC/TMD criteria for either headache attributed to TMD, myalgia of the temporalis or both. Of these, two had a diagnosis of headache attributed to TMD, 16 of myalgia of the temporalis, and 71 were diagnosed with both. In 97.3% of the times that headache attributed to temporomandibular disorders was diagnosed, the patient was also diagnosed with myalgia of the temporalis. The Jaccard index was 0.8, indicating a substantial overlap between the two diagnoses. Finally, the overlap of pain location between the two diagnoses was substantial, with a Jaccard index of 0.9. Conclusions In the present study, headache attributed to temporomandibular disorders was almost exclusively diagnosed together with myalgia of the temporalis. Therefore, we propose that headache attributed to temporomandibular disorders and myalgia of the temporalis muscle have more clinical similarities than differences and as such could be considered one single clinical entity. Further studies will be needed to address the clinical consequences of this proposal.

Background Headache is identified as a common post‐COVID sequela experienced by COVID‐19 survivors. The aim of this pooled analysis was to synthesize the prevalence of post‐COVID headache in hospitalized and non‐hospitalized patients recovering from SARS‐CoV‐2 infection. Methods MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers, were searched up to 31 May 2021. Studies or preprints providing data on post‐COVID headache were included. The methodological quality of the studies was assessed using the Newcastle‐Ottawa Scale. Random effects models were used for meta‐analytical pooled prevalence of post‐COVID headache. Data synthesis was categorized at hospital admission/symptoms' onset, and at 30, 60, 90, and ≥180 days afterwards. Results From 9573 studies identified, 28 peer‐reviewed studies and 7 preprints were included. The sample was 28,438 COVID‐19 survivors (12,307 females; mean age: 46.6, SD: 17.45 years). The methodological quality was high in 45% of the studies. The overall prevalence of post‐COVID headache was 47.1% (95% CI 35.8–58.6) at onset or hospital admission, 10.2% (95% CI 5.4–18.5) at 30 days, 16.5% (95% CI 5.6–39.7) at 60 days, 10.6% (95% CI 4.7–22.3) at 90 days, and 8.4% (95% CI 4.6–14.8) at ≥180 days after onset/hospital discharge. Headache as a symptom at the acute phase was more prevalent in non‐hospitalized (57.97%) than in hospitalized (31.11%) patients. Time trend analysis showed a decreased prevalence from the acute symptoms’ onset to all post‐COVID follow‐up periods which was maintained afterwards. Conclusion This meta‐analysis found that the prevalence of post‐COVID headache ranged from 8% to 15% during the first 6 months after SARS‐CoV‐2 infection., Headache is a common acute symptom of COVID‐19 and also a common post‐COVID‐19 symptom. The prevalence of post‐COVID headache ranged from 8% to 15% during the first 6 months after SARS‐CoV‐2 infection.

There are 13 species of Jmiperus found west of the Mississippi River. The distribution of these small trees and shrubs was largely confined to steep, rocky fire-proof sites prior to European colonization. Since then, junipers have greatly expanded their distribution as fire frequencies and competition from herbaceous species were reduced. Climatic trends, allelochemic properties of litter, and animal dispersal may also be involved in these expansions and thickenings. Increases in trees were followed by diminishment of understories and accelerated soil erosion. Because juniper tissue is utilized by very few herbivores and detritivores, juniper dominance can persist for centuries unless man intervenes. Unfortunately, understoiy fine fuels are usually now too sparse to use prescribed burning. Soil seed reserves of desirable forages are also usually depleted. Thus, the most common treatments during the 1950s and 1960s were chaining or cabling followed by seeding of desirable forage plants. The longevity of these treatments depends on the thoroughness of the initial treatment and subsequent management. Enhanced environmental awareness in recent decades has voided further application has of these treatments on public lands. Increased costs for treatments and lowered demands for red meat have limited type conversions on private lands. Although herbicides are available to kill mature junipers, the amounts required make them too expensive for Table 32.1 Common and scientific names of all species of junipers (Juniperus spp.) naturally occurring in the U. S. west of the Mississippi river. * = those resprouting after fire (1). Common name Scientific name Western States Where They Occur Ashe juniper J. ashei Buchholz TX, OK, MO, AK California juniper J. California Carr CA, NV, AZ common juniper *J. communis L. WA, OR, CA, ID, NV, MT, WY, UT, AZ, CO, ND, SD, NM alligator juniper *J. deppeana Steud. AZ, NM, TX drooping juniper J. flaccida Schlecht TX creeping juniper *J. horizontalis Moench MT, WY, ND, SD one seed juniper J. monosperma (Engelm.) Sarg. AZ, NM, CO, TX, OK western juniper J. occidentalis Hook WA, OR, CA, NV, ID Utah juniper J. osteosperma (Torr.) Little CA, NV, ID, WY, MT, UT, CO, AZ, NM redberry juniper J. pinchotii Sudw. TX, NM, OK Rocky mountain juniper J. scopulorum Sarg. WA, OR, NV, ID, MT, WY, UT, AZ, CO, TX, ND, SD, NE southern redcedar J. silicola (Small) Bailey TX, LA eastern redcedar J. virginiana L. ND, SD, NE, KS, OK, TX, AK, MO, IA, LA 326 common use. Meanwhile, increased sediment production continues and water yields decline from juniper-dominated watersheds. Midsummer fire storms are beginning to convert dense stands to dominance by introduced annuals or warm season sod grasses. Recurring fires generally lead to site degradation. Proactive management, especially on the federal lands, is presently almost nil. Further reductions or even complete removal of livestock will have very little effect on this regional problem and wildfires may even be encouraged. Without more substantial financial return from the wood, there is little hope for treating mature juniper stands. We can, however, use prescribed burning where it is still possible, promptly reseed after wildfires, and retreat the earlier chainings and cablings that are going back to trees.

This study aims to evaluate the functional variations of the electromyographic response and clinical symptomatology in TMD patients. This study has been performed and compared before and after the application of a therapeutic protocol based on the use of an oral device working on the proper mandibular repositioning through the proprioceptive-based lingual re-education called “Lingual Ring”. Between January to December 2016, 32 TMD patients have been recruited out of a series of 321 individuals recruited at the Neurosensorial and Motorial Surgery Department, in Palermo (Italy). All the patients underwent the Surface Electromyography (sEMG) of Masseter and Temporal muscles, with different registrations at T0, T1, T2, and T3, to evaluate the variations of the Electromyographic values, it was assigned the application of the Lingual Ring as the only therapy. The study demonstrated a neat rebalancing of the EMG tracks and important improvements with the TMD related issues. The clinical responses, due to the treatment at the end of the therapeutic protocol, were: absence or reduction of muscular or articular pain, absence or reduction of articular noises, absence or reduction of the cephalalgia. Hence, significant results, both clinical and in terms of instrumental EMG, were assessed. We can affirm that the adopted methodology allowed the monitoring of the Electromyographic variation and clinical symptoms. Moreover, the usage of the “Lingual Ring device” allowed to carry out a simple and immediate therapeutic protocol that is minimally invasive, ensuring a clear rebalancing of the EMG tracks as well as the TMD related pain.

Malaria is a febrile and potentially fatal infection. It is typically transmitted to humans through the bite of Anopheles mosquitoes and less frequently can be contracted through blood transfusions, sharing contaminated needles and syringes, mother-to-child transmission, or after solid organ transplantation. Posttransplant malaria has rarely been reported in the literature, even in endemic areas. We report the cases of three solid organ recipients in which Plasmodium vivax infection was documented during postsurgical evaluation 30 days after transplant surgery. The diagnosis of donor-derived malaria was confirmed in all patients by demonstrating Plasmodium in a peripheral blood smear and by polymerase chain reaction (PCR). All recipients had symptoms. The liver transplant recipient had myalgia, arthralgia, and thrombocytopenia; the kidney transplant recipient developed acute renal failure; and the heart transplant recipient had fever, cephalalgia, and tonic-clonic seizures. Pre-transplant screening of donors and recipients from endemic regions may not be sufficient to safely rule out persistent malaria. In Colombia, according to legislation, no mandatory testing is required for the diagnosis of malaria in organ donors in nonendemic areas. Therefore, donor screening by questionnaire is the only tool for preventing transplant-borne malaria. The migratory trend from Venezuela to Colombia has increased the number of imported cases of malaria, and the infection may be present in endemic and nonendemic regions. Although donor evaluation is not standardized in current guidelines, we suggest that donors be tested for malaria with a peripheral blood smear, detection of specific IgG antibodies against Plasmodium, and techniques such as PCR, if possible.

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody positive utilateral cerebral cortical encephalitis (UCCE) comprises a new entity with heterogeneity which usually present as epilepsy. Cases with cephalalgia as the only clinical feature were rare reported. Here, We report a case with MOG antibody positive UCCE who only presented with refractory cephalalgia and had a good response to glucocorticoid. MOG antibody-related UCCE should be identified when patients present with refractory headache and it may represent benign cortical encephalitis.Case Presentation: The case of a 41-year-old woman with MOG antibody positive UCCE presented with refractory cephalalgia. Neurological examination is normal, and fundus examination suggested bilateral optic nerve head edema. Brain MRI discovered Flair hyperintense lesions in the sulci of right temporoparietal occipital cortex. MOG antibody was positive both in the serum and cerebrospinal fluid. When the patient was treated with intravenous methylprednisolone, her headache completely disappeared and brain MRI showed partly recovery. At the follow-up of 6 months after discharge, she had no relapse, serum MOG antibody was negative and the high signal intensity on Flair had completely disappeared.Conclusions: MOG antibody-positive UCCE with headache as the single clinical symptom may represent benign cortical encephalitis.

Ethnopharmacological relevance Trillium tschonoskii Maxim. is one of traditional Chinese medical herbs that has been utilized to treat brain damages and cephalalgia. The neuroprotective effect of total saponins from Trillium tschonoskii rhizome (TSTT) has been demonstrated efficacy in rats following ischemia. However, the axonal remodeling effect of TSTT and the detailed mechanisms after ischemic stroke have not been investigated. Aim of the study We aimed to estimate therapeutic role of TSTT in axonal remodeling using magnetic resonance imaging (MRI) technique, and explored possible mechanisms underlying this process followed by histological assays in ischemic rats. Methods Male Sprague-Dawley (SD) rats underwent permanently focal cerebral ischemia induced by occluding right permanent middle cerebral artery. TSTT was intragastrically administrated 6 h after surgery and once daily for consecutive 15 days. Neurological function was assessed by the motor deficit score and beam walking test. T2 relaxation mapping and diffusion tensor imaging (DTI) were applied for detecting cerebral tissues damages and microstructural integrity of axons. Luxol fast blue (LFB) and transmission electron microscope (TEM) were performed to evaluate histopathology in myelinated axons. Double immunofluorescent staining was conducted to assess oligodendrogenesis. Furthermore, the protein expressions regarding to axonal remodeling related signaling pathways were detected by Western blot assays. Results TSTT treatment (65, 33 mg/kg) markedly improved motor function after ischemic stroke. T2 mapping MRI demonstrated that TSTT decreased lesion volumes, and DTI further confirmed that TSTT preserved axonal microstructure of the sensorimotor cortex and internal capsule. Meanwhile, diffusion tensor tractography (DTT) showed that TSTT elevated correspondent density and length of fiber in the internal capsule. These MRI measurements were confirmed by histological examinations. Notably, TSTT significantly increased Ki67/NG2, Ki67/CNPase double-labeled cells along the boundary zone of ischemic cortex and striatum. Meanwhile, TSTT treatment up-regulated the phosphorylation level of Ser 9 in GSK-3β, and down-regulated phosphorylated β-catenin and CRMP-2 expression. Conclusion Taken together, our findings indicated that TSTT (65, 33 mg/kg) enhanced post-stroke functional recovery, amplified endogenous oligodendrogenesis and promoted axonal regeneration. The beneficial role of TSTT might be correlated with GSK-3/β-catenin/CRMP-2 modulating axonal reorganization after ischemic stroke.

Acute basilar artery occlusion (BAO) is an uncommon cause of stroke; however, it constitutes a serious medical emergency and is associated with elevated mortality rates as well as unfavorable functional outcomes. This is especially true when it is not rapidly diagnosed, and the initiation of reperfusion therapies is delayed. Its etiology is mainly embolic or atherosclerotic, and it often presents with non-specific signs and symptoms (e.g., vertigo, cephalalgia, reduced consciousness, or hemiparesis) that can simulate an anterior circulation stroke. Therefore, obtaining imaging studies that include computed tomography (CT), computed tomography angiography (CTA), and diffusion-weighted magnetic resonance imaging (DWI MRI) as part of the diagnostic approach is crucial to make an accurate diagnosis. The main pillar of acute BAO treatment is early recanalization using intravenous thrombolysis, mechanical thrombectomy, or bridging therapy, in which both methods are used. This pictorial essay illustrates the essential role that multimodal imaging plays in the prompt diagnosis, management, and overall outcome of patients with acute BAO.

The treatment of cluster headache has evolved to include a handheld neuromodulation device and a monoclonal antibody in addition to more traditional agents. Galcanezumab is an approved treatment for episodic cluster headache. The non-invasive vagal nerve stimulator has been shown to be effective as a treatment for episodic cluster headache. Dedicated pituitary imaging may not be necessary with a normal MRI of the brain. Cluster headache is the most common trigeminal-autonomic cephalalgia, characterized by unilateral, frequent, debilitating attacks associated with ipsilateral autonomic symptoms. Attacks have a circadian and, often, seasonal pattern with periods of remission that can last months to years in episodic patients. Though a rare disease, an increasing number of studies have revealed novel targets for treatment. Treatment in cluster headache should focus on early intervention to reduce frequency of attacks and the length of the cycle, which improves outcomes and disability. Acute therapy is used to treat attacks, while bridging and preventive therapies are combined to reduce cycle length. Case 1: A 43-year-old man presents with the chief complaint of severe headaches. Upon general examination, he seems uncomfortable, agitated, and exhausted. He states that he hasn’t “slept in over a week because of debilitating headaches.” His headaches start around the same time every night: when he lays down to go to sleep. The pain is described as sharp, like a “hot poker” to his left eye. His partner has noticed that his eye droops and turns red when the pain starts. The attacks come on abruptly and prevent him from sleeping. The severe pain lasts 30 to 45 min, but he has mild-to-moderate pain that lingers for the rest of the night. He has seen his primary care physician, an allergist, and an ear, nose, and throat (ENT) specialist before coming to see a neurologist. Similar headaches occurred last year during the month of October as well. On further questioning, he reports that these headache attacks have been occurring almost yearly for the past 7 years. Each year, these headaches come on as the weather is changing and occur on a nightly basis for about 3 to 4 weeks.

Background Patients with acute aneurysmal subarachnoid hemorrhage (aSAH) experience excruciating headache that is difficult to manage in resource-constrained settings. Pregabalin’s (β-isobutyl-GABA) analgesic, antiepileptic, and antiemetic properties make it an attractive adjuvant in pain management for these patients. Methods We conducted a double-blind, placebo-controlled, randomized clinical trial on 40 aSAH patients undergoing aneurysmal clipping to assess the effect of perioperative pregabalin in decreasing perioperative headache, anesthetic, and opioid requirement. Patients received either pregabalin (75 mg) or placebo twice daily soon after admission till 24-hour postoperative, in addition to paracetamol 650 mg thrice daily. Headache assessed using a visual analog scale (VAS) at five time points was compared using a mixed effects regression model. Results Pain assessed by VAS declined significantly more from the baseline in pregabalin recipients compared with placebo at preinduction (–3.6 vs.–1.8; p = 0.004), 12-hour (4.3 vs. 2.8; p = 0.014), and 24-hour postsurgery (4.7 vs. 2.9; p = 0.007), but not at the 6-hour postoperation (4.9 vs. 3.8; p = 0.065). Pregabalin recipients required a lower minimum alveolar concentration of sevoflurane to maintain a prespecified bispectral index of 40 and 60 (0.8 vs. 0.9; p = 0.014) and required fewer rescue analgesic doses in the 24 hours following surgery (1.8 vs. 3.3; p = 0.005). The intraoperative fentanyl requirement was not significantly different between the groups (10 μg/kg vs. 11.4 μg/kg; p = 0.065). There was no significant difference in the sedation scores. Conclusions Pregabalin 75 mg administered twice daily, during the perioperative period, was an effective adjunct in the management of the severe headache experienced by patients with aSAH and decreased the opioid and anesthetic requirement without significantly increasing sedation.

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.

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.

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.

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.

Pi&ntilde, on (Pinus spp. L.)&ndash, juniper (Juniperus spp. L.) woodlands&rsquo, historical stand structures were recreated to provide reference conditions and document long-term changes in the Sky Islands of the Davis Mountains, Texas. Restoration of these isolated woodlands requires insights into the range of variability in current and historical stand structures, as well as an understanding of the spatiotemporal establishment and recruitment patterns of tree species. With drastic changes in forests and woodlands of the Southwestern United States widely reported, the main objective of this study was to reconstruct woodland tree temporal and spatial establishment patterns. A stratified random sampling approach was used to select two study sites each of 3600 m2 in area. Within each site, all individual trees were mapped, measured, and cored for age determination. Age and tree location data were used to recreate the spatiotemporal patterns of tree species establishment and recruitment. Increments in density of both Mexican pi&ntilde, on (Pinus cembroides var. cembroides Zucc.) and alligator juniper (Juniperus deppeana var. deppeana Steud.) reached 422 trees ha&minus, 1 in the 115-year period between 1890 and 2005, a yearly increment of 4 trees ha&minus, 1 that did not reflect a rapid rate of change in these pi&ntilde, on&ndash, juniper woodlands. Age distributions reflected the multi-cohort nature of these woodlands, and spatial autocorrelation measures were useful in the objective delineation of these cohorts. Temporal and functional niche differentiation of juniper was reflected in the development pattern where alligator juniper served as a pioneer species, exhibited a longer period of substantial recruitment, and had greater recruitment rates than that of Mexican pi&ntilde, on. Recruitment of Mexican pi&ntilde, on and alligator juniper occurred in an episodic fashion, with the majority of recruits being acquired between 1890 and 1949.

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.

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.

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.

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.

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.

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.

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 To investigate the relationship between primary headache types and accomplished or attempted suicide in countries from all world regions. Methods Data were obtained using a questionnaire about suicide due to headache in a face-to-face interview with 203 physicians with expertise in headaches. They came from 48 countries, and from all continents. Results Primary headaches cause one suicide per 1,000,000 population each year (1% of the suicide rate due to all causes). Cluster headache and migraines account for 70–80% of them. Suicide attempts are 10 times more frequent than accomplished suicides. Cluster headache poses more risk than migraine. This risk is not often acknowledged, and is increased if there is previous psychiatric history. More than half of the physicians interviewed think it could be reduced with a more aggressive treatment of headaches. Conclusions Cluster headache and migraine are not always benign, and are the cause of the majority of suicides due to headache.