A Review on Headaches Due to COVID-19 Infection.

Since December 2019, the time when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spotted, numerous review studies have been published on COVID-19 and its neuro invasion. A growing number of studies have reported headaches as a common neurological manifestation of COVID-19. Although several hypotheses have been proposed regarding the association between headache and the coronavirus, no solid evidence has been presented for the mechanism and features of headache in COVID-19. Headache also is a common complaint with the omicron variant of the virus. COVID-19 vaccination also is a cause of new-onset headaches or aggravation of the previous headache in migraine or tension headache sufferers. In this review study, the types of headaches reported in previous studies and their possible pathogenic mechanisms are outlined. To accomplish this objective, various types of headaches are classified and their patterns are discussed according to ICHD-3 diagnostic criteria, including, headaches attributed to systemic viral infection, viral meningitis or encephalitis, non-infectious inflammatory intracranial disease, hypoxia and/or hypercapnia, cranial or cervical vascular disorder, increased cerebrospinal fluid (CSF) pressure, refractive error, external-compression headache, and cough headache. Then, their pathogeneses are categorized into three main categories, direct trigeminal involvement, vascular invasion, and inflammatory mediators. Furthermore, persistent headache after recovery and the predictors of intensity is further investigated. Post-vaccination headache is also discussed in this review.

Tension-type headache.

Tension-type headache (TTH) is the most prevalent neurological disorder worldwide and is characterized by recurrent headaches of mild to moderate intensity, bilateral location, pressing or tightening quality, and no aggravation by routine physical activity. Diagnosis is based on headache history and the exclusion of alternative diagnoses, with clinical criteria provided by the International Classification of Headache Disorders, third edition. Although the biological underpinnings remain unresolved, it seems likely that peripheral mechanisms are responsible for the genesis of pain in TTH, whereas central sensitization may be involved in transformation from episodic to chronic TTH. Pharmacological therapy is the mainstay of clinical management and can be divided into acute and preventive treatments. Simple analgesics have evidence-based effectiveness and are widely regarded as first-line medications for the acute treatment of TTH. Preventive treatment should be considered in individuals with frequent episodic and chronic TTH, and if simple analgesics are ineffective, poorly tolerated or contraindicated. Recommended preventive treatments include amitriptyline, venlafaxine and mirtazapine, as well as some selected non-pharmacological therapies. Despite the widespread prevalence and associated disability of TTH, little progress has been made since the early 2000s owing to a lack of attention and resource allocation by scientists, funding bodies and the pharmaceutical industry.

Sumatriptan Does Not Antagonize CGRP-Induced Symptoms in Healthy Volunteers.

OBJECTIVE: Previous attempts to develop a pragmatic human model for testing new anti-migraine drugs, have failed. Calcitonin gene-related peptide (CGRP) induces a mild headache in healthy volunteers and migraine-like headache in migraine patients. The induced headache must respond to already established migraine treatment for validation. Thus, the objective of the study was to test the effect of sumatriptan against CGRP-induced symptoms in an attempt to validate CGRP-induced headache as a model for drug testing. METHODS: Thirty healthy volunteers were recruited to receive a 2-hour infusion of CGRP on 2 separate days. The participants were pretreated with sumatriptan 1 day and with placebo the other day in a randomized double-blind cross-over fashion. During the infusion, a questionnaire about headache and side effects was administered. Electrocardiography, heart rate, blood pressure, dermal blood flow, and diameter of peripheral arteries were monitored during the infusion. Participants were carefully instructed to fill out a headache questionnaire at home until 12 hours after the infusion start. Primary endpoints are difference between the sumatriptan day and the placebo day in area under the headache score curve (AUC) 0-2 hours after infusion start and in headache intensity 2 hours after infusion start. The study was conducted at the Danish Headache Center in Glostrup, Denmark. RESULTS: CGRP-induced headache in 86% (25/29) of the participants on the sumatriptan day and in 96% (28/29) of the participants on the placebo day. There was no difference in AUCheadache, 0-2 hours between the days (P = .794). There was a statistically significant decrease in mean atrial pressure (MAP) over time on both days with a16.2% reduction on the sumatriptan day and a 14.8% reduction on the placebo day (P < .001) and a statistically significant increase in heart rate (HR) over time on both days (from mean 57.5 at baseline to mean 105.4 at 120 minutes on the sumatriptan day and from mean 60.2 at baseline to 105.8 at 120 minutes on the placebo day, P < .001). The diameter of peripheral arteries increased statistically significant on both days (P < .001). CONCLUSION: Sumatriptan does not influence headache score, accompanying symptoms or other symptoms induced by CGRP. Furthermore, a 2-hour CGRP infusion causes a wide range of side effects and does not induce more headache than the usual 20-minute infusion. Thus, the prolonged infusion of CGRP in healthy volunteers is not a valid and pragmatic model for testing new anti-migraine drugs.

Personalized image-based tumor growth prediction in a convection-diffusion-reaction model.

Inter-individual heterogeneity of tumors leads to non-effectiveness of unique therapy plans. This issue has caused a growing interest in the field of personalized medicine and its application in tumor growth evaluation. Accordingly, in this paper, a framework of personalized medicine is presented for growth prediction of brain glioma tumors. A convection-diffusion-reaction model is used as the patient-specific tumor growth model which is associated with multimodal magnetic resonance images (MRIs). Two parameters of intracellular area fraction (ICAF) and metabolic rate have been used to incorporate the physiological data obtained from medical images into the model. The framework is tested on the data of two cases of glioma tumors to document the approach; parameter estimation is made using particle swarm optimization (PSO) and genetic algorithm (GA) and the model is evaluated by comparing the predicted tumors with the observed tumors in terms of root mean square error of the ICAF maps (IRMSE), relative area difference (RAD) and Dice's coefficient (DC). Results show the differences of IRMSE, RAD and DC in 4.1 ∓ 1.15%, 0.099 ∓ 0.041 and 85.5 ∓ 7.5%, respectively. Survival times are estimated by assuming the tumor radius of 35 mm as the fatal burden. Results confirm that less-diffusive tumors lead to higher survival times. The represented framework makes it possible to personally predict the growth behavior of glioma tumors only based on patients' routine MRIs and provides a basis for modeling the personalized therapy and walking in the path of personalized medicine.

Migraine with brainstem aura: defining the core syndrome.

Migraine with brainstem aura is a rare subtype of migraine with aura. Although this entity has been known for many years, its diagnosis and even its existence are still a matter of debate. Previous studies demonstrated that current diagnostic criteria for migraine with brainstem aura are too open and brainstem symptoms may originate within the cortex and not in the brainstem. The aims of the present study were to analyse whether aura from the brainstem exists, how prevalent such a core syndrome is, to analyse if current diagnostic criteria define such a core syndrome and, if necessary, to develop new diagnostic criteria that define only the core syndrome. We analysed all migraine with brainstem aura cases described in detail in the literature, clinical cases from the Danish Headache Center (DHC) and our large sample of telephone interviewed cases with migraine with aura. We selected the 20 most convincing cases from the literature and convincing cases from the DHC. Of 79 migraine with brainstem aura cases described in detail in the literature, 44 fulfilled the diagnostic criteria for migraine with brainstem aura of the International Classification of Headache Disorders, 3rd edition (ICHD-3). In the DHC after face-to-face interview, neurological examination and imaging, four migraine with brainstem aura of 293 cases with migraine with aura (1.37%) were found, corresponding to 0.04% of the general population. The 20 most convincing cases had symptoms that likely originated in the brainstem. Our telephone-interviewed cohort included 1781 subjects with a diagnosis of migraine with aura or probable migraine with aura. Of these, 228 fulfilled the diagnostic criteria for migraine with brainstem aura of the ICHD-3. Thus, using telephone interview diagnosis according to current diagnostic criteria results in too many cases of migraine with brainstem aura being diagnosed. Therefore, we developed stricter diagnostic criteria in an attempt to include only those rare cases that definitely have aura originating from the brainstem. Migraine with brainstem aura does exist, but it is very rare. Existing diagnostic criteria are too unspecific, but it was possible to develop tighter criteria that define a core syndrome probably caused by brainstem dysfunction.

New daily persistent headache: a systematic review on an enigmatic disorder.

BACKGROUND: New daily persistent headache (NDPH) presents with a sudden onset headache which continues without remission within 24 h. Although rare, NDPH is important because it is one of the most treatment refractory primary headache disorders and can be highly disabling to the individuals. In this structured review, we describe the current knowledge of epidemiology, clinical features, trigger factors, pathophysiology, diagnosis and therapeutic options of NDPH to better understand this enigmatic disorder. The prevalence of NDPH estimated to be 0.03% to 0.1% in the general population and is higher in children and adolescents than in adults. Individuals with NDPH can pinpoint the exact date their headache started. The pain is constant and lacks special characteristics but in some has migraine features. The exact pathogenic mechanism of NDPH is unknown, however pro-inflammatory cytokines and cervicogenic problems might play a role in its development. The diagnosis of NDPH is mainly clinical and based on a typical history, but proper laboratory investigation is needed to exclude secondary causes of headache. Regarding treatment strategy, controlled drug trials are absent. It is probably best to treat NDPH based upon the predominant headache phenotype. For patients who do not respond to common prophylactic drugs, ketamine infusion, onabotulinum toxin type A, intravenous (IV) lidocaine, IV methylprednisolone and nerve blockade are possible treatment options, but even aggressive treatment is usually ineffective. CONCLUSION: NDPH remains poorly understood but very burdensome for the individual. Multi-center randomized controlled trials are recommended to gain better understanding of NDPH and to establish evidence based treatments.