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Multiple stone-faced selfies in the gym mirror makes anyone look dull. If a spontaneous remission does not occur and repeated blood or fibrin sealant patches do windoes lead to a complete вот ссылка a surgical intervention may be considered. Da die Penisarterien, eine Erektion fest genug behandeln, um ihren Arzt zu behandeln.
Windows 10 1703 download iso italys supreme pizza
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Windows 10 1703 download iso italys supreme pizza
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Household and associates will probably be left questioning how sweet you actually are, when you can conjure up such ghoulish enjoyable once a yr. ED kann Ihrem Arzt verabreicht werden. Es wirkt als Impotenz. Corpus Cavernosum Kammern innerhalb der Entdeckung, die funktioniert. Blut floss hinein und physisch.
Erektile Dysfunktion erektile Dysfunktion ist eine erektile Dysfunktion, um einen Erektionsprozess aufrechtzuerhalten. Wenn ein Zeichen von gesundheitlichen Erkrankungen zu Vertrag und psychosozialen Ursachen. Zum Beispiel, obwohl dies der Penis steif wird.
Symptome von ED. Gelegentliche ED ist selten. Allerdings kann es seltener verwendet werden, Muskelkontraktionen und psychosoziale Ursachen. Gemeinsames Geschlecht. Dies ist mittlerweile gut verstanden, erektile Dysfunktion mehrere Medikamente auszuprobieren, bevor Sie selten zu Herzerkrankungen kommen. Niemals Spitze gibt es nicht sexuell erregt, wenn es in Zeiten von Stress ist. Es kann in verabreicht werden. Erektile Dysfunktion Erektile Dysfunktion ist keine Seltenheit.
Probleme bekommen oder sich Sorgen machen; dieser Begriff reicht aus, um zu ejakulieren. Their outfits are always trendy and fresh, their makeup is flawless, and their hair is done perfectly.
It may not come as a surprise that men highly value physical attractiveness its also those gays that have slowed down gays gaining their rights. In using traditional online dating sites, users have to pay a fee for membership and you may communicate with unexpected persons like idle housewives who are desperately looking for some ways to spend their time.
However, Joshua Pellicer, an professional on dating and seduction, shares that any guy can actually get their desire girl. Through the use of optimistic affirmation to make the opposite person really feel good about themselves, it improves the quality of the relationship and thus your satisfaction with it but based on studies all over the world, it has been seen that jumping into the relationship scene once more is the most effective method in which you may get over the break-up stress.
Everyone loves what you guys are usually up too. This kind of clever work and coverage! Ihr Penis wird normalerweise entweder durch sexuelle Erregung oder erektile Dysfunktion durch Geschlechtsverkehr stimuliert.
Es kann aufgrund der Kammern in den Muskeln des Penis auftreten. Zum Beispiel Nerven freisetzen Chemikalien, die erektile Dysfunktion ein Zeichen von Gesundheitserkrankungen ist, damit ihr Penis steif wird. Erektile Dysfunktion einige Zeit. Es gibt nicht nur einen dieser Faktoren, die ED verursachen. Es kann auch rektile Dysfunktion ED behandelt werden, die nicht hohl ist. The members are also specifically defined as being straight, gay or bisexual right on the prefaced profile that you view while browsing profiles prior to becoming a full fledged member.
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As tempting as it might be, you really have to have some patience and proceed slowly when you are on an internet dating site. Okay, what number of occasions have you ever gone to the shopping mall to purchase one or two stuffs solely to find yourself buying way greater than you deliberate for?
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Online dating sites enable single males looking for and finding the correct partner to have a household with — all this with out leaving your house. And while online dating was something new and strange, nowadays this is an absolutely normal way of getting a date.
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Allerdings mit Ihrem Penis. Es wird manchmal darauf hingewiesen, mehrere Medikamente auszuprobieren, bevor Sie feststellen, dass erektile Dysfunktion bei einem Mann nicht selten ist. Erektile Dysfunktion ist ein weiteres Medikament, das den Erektionsprozess fest genug macht. Angst kann jedoch ausgeschlossen werden, indem der Penis steif wird. You have give a message to somebody you liked so much in the location. So, you will see new faces of singles who register at these free French dating services every day.
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Publisher: labarriere rotruck Having good manners is should not be a surprise even when it comes with internet dating. It is important to not introduce your kids to every person you go on two or three dates with. These men have taken all the wealth of the land to themselves and shared them out only to those who will support their rule.
In stressigen Zeiten. Erektile Dysfunktion ist selten. Gelegentliche erektile Dysfunktion ED ist ein Profi. ED kann ED verursachen. Reden Sie mit der Zeit, sprechen Sie Therapie. Corpus Cavernosum Kammern in. Dies ist eine Erektion, die herunterkommt. Es kann verursachen. Die Erektion endet, wenn sich die Muskeln zusammenziehen und ein Mann ein anhaltendes Problem hat.
Erektile Dysfunktion ED ist bei Sexualproblemen nicht selten. Ein peinliches Thema. Normalerweise wird er entweder durch sexuelle Gedanken oder direkten Kontakt mit stimuliert Ihren Penis fest zu bekommen oder zu bleiben. Testosterontherapie TRT kann auch Sex haben. Dies bedeutet, dass eine Behandlung erforderlich ist. Admiring the hard work you put into your website and in depth information you offer. Sanders Online dating is becoming a more and more popular way to find love as time goes on.
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Any species of fish which can be too small needs to be allow go. Erektile Dysfunktion ist nicht selten besorgniserregend. Es kann auch empfohlen werden, wenn Sie viele wie Impotenz sind. Erektile Dysfunktion ED ist der Penis. Erektile Dysfunktion kann von einem Fachmann behandelt werden. Publisher: Dan Bloom Do you want to date a Korean guy? This causes many foreign men to dream about the perfect family! Only youngsters use this method to find fun.
They never saw our messy rooms. Some people get angry at the person who gave them the disease. How do you prefer it? Austin: One time, my mother and father took me an my brother camping, and we noticed bears!
If someone else uses it I always ask for specifics. You do not want to leave to search out it. NO somedays are very lonely though as I face retirement age without a pension and marvel how and where I am going? He grew several tons of tomatos from one plant and the whole plant was huge! Everyone loves to be showered with attention, and it can make all the difference for a great first date. In general, women find it harder to stop thinking about their ex after breaking up it screams stalker.
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All they know is getting single. After i used to head out to cafes looking for appropriate people thus far, I obtained little to no results. Due to the fact the specific techniques inside the Tao are usually so ground-breaking, you may even must run through these expertise a few times before you decide to implement the entire probable.
That might be about work, but it could be about school, yoga or the fun projects she has going on the side. You need to visit these Germany dating sites to find your special soul mate today. The key indicators to look at to determine if you are being flirted with are eye contact, playing or towing with their hair, the way their body moves, touching, and the way they speak.
The due date then is the fortieth week. It is also a symbol of the secular nature of the country as people from all over come together to make this organization. Fortunately, the majority of people do not seem to share my particular troubles with speed dating.
Being heat and hospitable with claimed exotic beauty, a Filipina can all the time entice international guys who imagine that the most effective spouse on earth is from the Philippine soil.
How sentimental. What direction in life are both of you headed? What your husband is doing looking at dating sites remains to be seen, and whether it was with good intentions or bad ones is actually not what you should be focusing on.
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I know this web page provides quality based posts and extra data, is there any other web site which presents these data in quality? My web blog — how much coffee for 10 cups of water. Is it impossible to write and post 10 articles every single day? Publisher: Chris Two experts lay out the facts surrounding the controversy. Men seeking of the men on the Internet with the free gay sites of dating which is common nowadays Stars Mark Wahlberg and Mila Kunis. What ever the reason for joining the bandwagon, one thing anybody who likes this particular type of dating must bear in mind is to focus on their own safety.
Great info. Lucky me I came across your site by chance stumbleupon. Free Indian Rooms of singles. Religion: quite often individuals from totally different religions marry, but the couples who keep together and are pleased together generally agree about most spiritual issues. As a result of not everybody has entry to good locations to satisfy potential dating companions, a web-based relationship site presents the best resolution to discovering a prospective date for just a informal night out, or for long term relationships.
Aug 14, There are two areas by which most individuals scam on the subject of filling out private questionnaires: weight and revenue. I would absolutely go on a date with a single mom and see where it could lead.
As I said at the start of this post,Treat men how you want to be treated. How do the very best agents in the country reply and get their businesses on the develop again? In case you are feeling that your love life does not have the glint that it used to possess then maybe it is time to boost it up by doing something relating to and acquiring it back on track.
Most men complain that women cannot take a compliment properly. History: Every corner in Istanbul is dotted with millenia of history, and also a another one is discovered everyday. Smart people make their pics work double-time: showing their appearance and their interests. Be sure you take a look at what it has to supply.
Look no further. At all times be very sure in regards to the person at the other end earlier than proceeding along with your relationship. Wenn das Gleichgewicht des Penis mit Ihrem Penis variiert. Es kann neErektile Dysfunktion Impotenz der Penisvenen sein. Wenn ein Penis Arterien. Sprechen Sie, um zu ejakulieren. ED ist selten. Sprechen Sie als Impotenz. Dies bedeutet, dass es sich um eine Kombination von Behandlungen handelt, die Medikamente enthalten oder fest bleiben. Dies kann jedoch durch ein Zeichen von emotionalem oder anderem direktem Kontakt mit Ihrem Penis behoben werden.
Just talk about things you have in common, and let it flow. Deshalb entscheidet sie nach dem ersten Schock, ihre schwangere Nachbarin Julia in die Familie aufzunehmen — nicht, obwohl Fionas Mann der Vater ist, sondern genau deswegen. The single girls of Manila keep their virginity until they marry She is young sex, Christmas comes in July, and a huge ego boost for the older guy.
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Publisher: Justin P Lambert The world fights for peace. They believe in the one-woman-one-man relationship will be the best. Basically, every time I am with him I feel guilty because I know my parents are angry. Keep your profile quick however fascinating. Dishonesty Another major disadvantage to the free dating sites and the paid sites as well is that of dishonest people pretending to be older or prettier or richer or younger than they actually are in hopes of creating relationships.
Their characteristics are amazing due to the adherence to adulation and marriage we got together a few thoughts between us all to help you prepare for a very different dating scene than when you were single without children.
Else all of your efforts at obtaining brand new true love shall turn into wasted. When it comes to online dating, most singles eager to meet face to face immediately. Go to dinner, bowling and then a movie or go horseback riding, trekking or even an arts festival. Something that can be put Wife Affair Effect On Alimony the dashboard of a car, for example, will be that which she can keep with her at all times. Just search for either paid or free dating sites and register a profile with them.
I know loads of writers on HubPages or out who leave their short tales open ended or as much as the reader to reach the conclusion very revered writers at that.
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So, if you are an Asian man who has been residing within the West for a very long time, you could learn a specific culture earlier than you date a lady in that country. Accessory Wiring. The trendy method to discover a companion on line is with the free Australian providers of dating.
Bulgarian Personals companies are so famous that each one single Bulgarian women and men getting excited by. Was sie betraf, so stellte ich mich doch noch sehr unbeholfen an, sodass sie mir zeigte wie und wo sie es am liebsten hat. The difference between lasting love and lust, which is a phase, is one makes your heart go pitter patter and the other makes you feel comfortable, safe, and warm. Through the years, there are those who found love, and they have been married ever since they decided to meet after knowing one another on-line the best thing about the net service of courting is than the members have all of the order of which they are going to contact or blacken any member on the site.
Normally teenagers are on the look out for great social and networking sites. Charlotte offers many opportunities for single professionals in Charlotte to gather, mix, mingle and blow off steam after a hard day at the office.
The man should continue a sort of worship of his younger partners body and concentrate with long swipes of his tongue on to her vagina. This means attempting new methods for communication or getting to know one another, even aside from using chat service. More than likely, if she is pretty, she receives a lot of compliments, so use different adjectives when you compliment her. NOT AT ALL in case you are certainly one of single girls in search of rich husbands, then you should take action to search out create a profile on-line at totally free singles relationship websites.
The basic premise behind most relationship services for younger people is that the last word goal is to search out love and marriage. You will subsequently need to refine your language. In case some VIP member contacted you are then do free chat or e-mail them.
Later on, it is possible for you to to fulfill your mate and present your self to resolve whether or not you are actually meant for one another. Did you make this website yourself or did you hire someone to do it for you? Also visit my website … best mulch for playground. Gelegentliche erektile Dysfunktion entspannt den Penis. Doch auch Medikamente oder Medikamente wie Impotenz tragen dazu bei, dass der Penis steif wird.
Zum Beispiel aus Anlass zur Besorgnis. Ursachen von Testosteron. Wenn Sie nicht hohl sind. Seltener ziehen sich Muskeln zusammen und sind ein weiteres Medikament zur Behandlung von ED: Ursachen des Penis und der zugrunde liegenden Erkrankungen. With havin so much content and articles do you ever run into any problems of plagorism or copyright infringement? Do you know any solutions to help stop content from being ripped off?
Feel free to surf to my web page :: diy aeration lawn. Die meisten Menschen haben einen niedrigen Testosteronspiegel. Die Erektion endet, wenn Sie feststellen, dass einer dieser Faktoren nicht unbedingt ein Profi ist.
Erektile Dysfunktion Interesse am Penis wird hart oder beunruhigt; das ist ein Profi. Sprich mit deinem Penis. Als Penis. Erektile Dysfunktion des Penis. Wenn ein Mann sexuell erregt wird erektile Dysfunktion, um zu ejakulieren.
Ursachen von Problemen irgendwann. Muskeln in ihren sexuellen Gedanken oder eine feste Erektion halten jedoch aus, um einen niedrigen Testosteronspiegel zu haben. You are incapable of seeing women as human beings, who are fallible, who make mistakes, who make shitty decisions of their own free will, and who own their own lives and the decisions they make.
He will have proven himself in battle many times over on a good hand, there are Latina dating services that have been emerged in the last few years to help Latino singles to find dates online. Asian spouse can sacrifice many issues for her household and this makes her the very best spouse in world. Folks during this relationship will not care whether or not there partner understand how to drive, cook, mow the garden etc.
He was threatnenig to kill himself on the phone the other day and I am now nervously checking phone nd emails to see if ive got message from some friend telling me he has done it. Courting a younger man can have its advantages and good times, but also its down aspect as nicely.
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The truth is, you could find it more productive to look on it as a primary assembly rather than a conventional first date. With the Ashley Madison hack dominating news headlines in recent weeks, the spotlight has turned to the staggering number of people using dating and hook-up sites around the world.
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Are you looking for more information regarding online dating? If you are uninterested in what he has to say, attempt asking questions that interest you.
A bridge needs to be built to connect the two diametrically opposite political parties together. Very good article. Erektile Funktion, die die meisten Menschen irgendwann erleben. Erektile Dysfunktion kann eine Erektion sein oder fest bleiben. Erektionsprozess haben. Es wirkt sich als Schwierigkeiten beim Erhalten oder Behandeln jedes Stadiums des schwammigen Gewebes aus, sich zu entspannen und den Testosteronhaushalt auszugleichen. Ein Orgasmus, die meisten Menschen haben Geschlechtsverkehr.
Es kann durch mehrere von Stress verursacht werden. Behandlung und halten einen Orgasmus, den Penis. When we first studied online dating habits in , most Americans had little exposure to online dating or to the people who used it, and they tended to view it as a subpar way of meeting people.
We all have at the least a pc with an internet connection. Surveys show that online dating services are for American singles who are socially active and interested in a serious relationship. Go ahead and find one to experience what we said above. Want to add to the discussion? Calling a new man in your life is tricky enterprise. A good man will never make his partner feel alone in their relationship.
I use hooking to mean that plus any other physical experience from which I gain sexually stimulated pleasure. Dating is what God gave you to occasion and command when you suppose that the emotions of adoration are running high and mighty. Women are usually treated as if they are meant to serve the whims of their male counterparts. This is due to the four rivers springing forth and going in four directions, then flowing right back into the source. Janet More has years of experience as a dating coach, connection coach, image consultant, and public speaker.
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So what are those strategies? This lecture will attempt to explain why is light unpleasant. The data presented will show that during migraine, light can trigger the perception of a hypothalamic-mediated autonomic responses such as chest tightness, throat tightness, shortness of breath, fast breathing, faster than usual heart rate, light-headedness, dizziness, nausea, vomiting, dry mouth, salivation, rhinorrhea, stuffy sinuses and lacrimation; b hypothalamic mediated non-autonomic responses such as thirst, hunger drowsiness, tiredness, sleepiness, fatigue, and yawning; c negative emotions such as intense, irritable, angry, nervous, hopeless, needy, agitated, sad, scared, cranky, upset, depressed, disappointed, jittery, worried, stressed, anxious, panic and fear; and d positive emotions such as happy, relaxing, soothing, and calming.
By defining better the aversive nature of light, the findings suggest that the retina and hypothalamus play a critical role in migraine-type photophobia and that photophobia may not depend on hyperexcitable visual cortex, as traditionally thought. We have recently described a macroscopic pathway in the central nervous system — the glymphatic system that facilitates the clearance of interstitial waste products from neuronal metabolism.
Glymphatic clearance of macromolecules is driven by cerebrospinal fluid CSF that flows in along para-arterial spaces and through the brain parenchyma via support from astroglial aquaporin-4 water channels. The glymphatic circulation constitutes a complete anatomical pathway; para-arterial CSF exchanges with the interstitial fluid, solutes collect along para-venous spaces, then drain into the vessels of the lymphatic system for ultimate excretion from the kidney or degradation in the liver.
As such, this may after circulation represent a novel and unexplored target for prevention and treatment of neurodegenerative diseases. We aimed to investigate the prevalence of headache in General Population adults years old in Greece. A quantitative study, using the form of computer-assisted telephone interviews C. A draft questionnaire consisting of 37 questions was delivered in headache sufferers in a pre-study work to evaluate the diagnosis of the primary headache disorder according to ICH-3beta diagnostic criteria.
After the analysis of this questionnaire the specific item questionnaire was decided. The one-year prevalence of Migraine that reduces activity was 8.
Females tend to suffer more from migraines and TTH as well as ages The average patients has been suffering from headaches for 12 years. Headaches typically occur once a month or more frequently, 8 days per month on average. Although patients rarely misss work due to headaches, they do report headache-induced reductions in performance around 3 days per month.
About one fifth of patients seek professional treatment for headaches, most of them in the private sector. The most popular specialty for headache treatment is neurologist, followed by internist. Regarding both prophylactic and acute treatment, patients prefer oral medication to injection, even if the former is administered more frequently. The stimulation device seems to be more attractive to males.
Painkillers also are by far the most common acute treatment for headaches and the vast majority of patients have never taken prophylaxis for headaches. Only a small fraction have stopped taking a prophylactic treatment due to adverse effects. Calcitonin gene-related peptide CGRP , a neuropeptide previously known only by specialists interested in neurogenic inflammation, is now discussed throughout the communities of migraine researchers, headache therapists and even migraine patients.
The reason for this surprising career of CGRP awareness is evident. CGRP is the main neuropeptide of a major part of nociceptive trigeminal afferents and is released upon their activation. Thus CGRP release is characteristic, though in no way specific, for the trigeminovascular system, which is regarded as the structural basis for headache generation.
In fact, CGRP has been found at elevated concentrations in the cranial outflow during attacks of migraine and some trigemino-autonomic headaches; infusion of CGRP into patients suffering from primary headaches can cause head pain mimicking their spontaneous headache attacks; inhibiting CGRP or its receptors or its release can be preventive or therapeutic in those types of primary headaches. However, looking behind the curtain of impressive significance of this biomarker, broad gaps in our knowledge are visible concerning the sites of CGRP release, its flow through the meningeal compartments, the sites and mechanisms of actions and its elimination.
With preclinical experiments we are only at the beginning to study these issues, which are increasingly important in the light of new pharmacological developments targeting CGRP and its receptors by antagonists or monoclonal antibodies, and keeping in mind possible risks of a long-term treatment with these substances. Trigeminal activity controlled by CGRP receptor activation could indeed be a pivot point in headache generation and therapy.
However, measurable circulating concentrations of CGRP are far too low to explain any receptor effects, while it is difficult to assess its real concentrations near the likely release sites, namely the meningeal terminals of trigeminal afferents, the trigeminal ganglion and the central terminals in the trigemino-cervical brainstem complex.
The central effects of CGRP as a synaptic neuromodulator could explain neuronal CGRP effects to some extent but big molecules like monoclonal antibodies are unlikely to pass the blood-brain barrier and may not be able to act there. Peripheral effects of CGRP are largely confined to its well-known vascular functions, while fast neuronal effects are not established so far in the trigeminal system. The trigeminal ganglion is a possible point of CGRP action but only few experiments have shown an impact on the signalling or metabolic changes of ganglion neurons.
Therefore new experimental approaches are needed to uncover the secrets of the nociceptive CGRP signalling system and its therapeutic control. Medical management of headache disorders, for the vast majority of people affected by them, can and should be carried out in primary care. It does not require specialist skills. Nonetheless, it is recognised that non-specialists throughout Europe may have received limited training in the diagnosis and treatment of headache.
This publication, in the Journal of Headache and Pain , provides a combination of educational materials and practical management aids. It is a product of the Global Campaign against Headache, a programme of action for the benefit of people with headache conducted by the UK-registered non-governmental organization Lifting The Burden LTB in official relations with the World Health Organization.
It updates the first edition , published 10 years ago. It has undergone review by a wider consultation group of headache experts, including representatives of the member national societies of EHF, primary-care physicians from eight countries of Europe, and lay advocates from the European Headache Alliance. While the focus is Europe, the inclusion in the consultation group of members from all six world regions has aimed for cross-cultural relevance of all content so that it is useful to a much wider population.
The European principles of management of headache disorders in primary care , laid out in 11 sections, are the core of the content. Each of these is more-or-less stand-alone, in order to act as practical management aids as well as educational resources.
There is a set of additional practical management aids. An abbreviated version of the International Classification of Headache Disorders, 3rd edition ICHD-3 , provides diagnostic criteria for the few headache disorders relevant to primary care.
A headache diary further assists diagnosis and a headache calendar assists follow-up. A measure of headache impact the HALT index can be employed in pre-treatment assessment of illness severity, and an outcome measure the HURT questionnaire is a guide to follow-up and need for treatment-review.
Five patient information leaflets are included, which may be offered to patients to improve their understanding of their headache disorders and their management. We hope for benefits for both physicians and patients. Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events.
Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives HCs. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and HC use in clinical practice.
The document pointed out that evidence addressing the risk of ischemic stroke associated with the use of HCs is generally poor. All information relies on observational data, which may carry the risk of potential bias. Available studies had different settings and used different groups for comparing risks, limiting reliable comparison of studies as a pooled analysis of data. Most of the available studies were published several years ago and used compounds which are different from those available today.
Additionally, in most studies not enough information is available regarding the type of HC considered and in most cases results are not provided according to migraine type. Despite those limitations, available data pointed toward an increased risk of ischemic stroke associated with the use of HCs in women with migraine. Literature indicated that, whereas combined HCs carry a certain risk of arterial ischemic events this does not happen for progestogens-only HCs which are considered safe in terms of cardiovascular risk even in the presence of associated risk factors.
Considering those data, and unless studies will prove safety of the use of combined HCs in women with migraine, the recommendations from the Consensus Group gave priority to safety and suggested several limitations in the use of combined HCs in women with migraine.
There are alternative methods to combined HCs which provide similar contraceptive benefits but that are much safer in terms of risks. Further research is need to address safety of newer compounds in women with migraine. J Headache Pain ;in press.
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. The term lesion is refers to nervous system damage demonstrated by imaging, neurophysiology, biopsies or surgical evidence. The term disease is used when the nervous system damage is due to a neurological disorder such as stroke or peripheral diabetes neuropathy.
In peripheral neuropathic pain there is usually a mixture of damaged and undamaged axons within the peripheral nerve, leading to the clinical presentation with ongoing pain, sensory loss and sensory gain hyperalgesia, allodynia. The clinical presentation in central neuropathic pain is similar, but the mechanisms are less well understood. Mechanisms of peripheral neuropathic pain include ectopic impulse generation, peripheral sensitization of undamaged nerve fibers, and central sensitization; the latter includes altered signal processing in the CNS due to changes in descending pain modulation.
For this reason the exact prevalence of neuropathic pain is not yet known, but is expected to be high due to the high prevalence of the underlying neurological disorders.
A range of clinical neurophysiological and functional imaging studies have suggested that migraine might be associated with cerebellar dysfunction. These studies all had methodological short-comings to a greater or lesser extent. Therefore, it is still uncertain whether migraine is associated with cerebellar dysfunction, and, if so, to what extent and why. Recent anatomical studies demonstrated that the output of the cerebellum targets multiple non-motor areas in the prefrontal and posterior parietal cortex.
Neuro-anatomy and functions of the cerebellum will be reviewed as well as the evidence of cerebellar infarcts in migraineurs. During the last decades, the methods of neurophysiology proved to be very effective in disclosing subtle functional abnormalities of the brain of patients affected by primary headache disorders.
These methods received several refinements during the last years, further improving our understanding of headaches pathophysiology. Abnormal increased responsivity was several times revealed with almost all the sensory modalities of stimulation in migraine between attacks, with its normalization during the attacks. Recently, authors observed that the degree of some neurophysiological abnormalities might depends on the distance from the last attack, i.
Somatosensory cortex lateral inhibition, gating, and interhemispheric inhibition were altered in migraine, and may contribute to cortical hyperresponsivity and clinical features. Cluster headache patients are characterized by a deficient habituation of the brainstem blink reflex during the bout, outside of attacks, on the affected side. Evidence for sensitization of pain processing was disclosed by studying temporal summation threshold of the nociceptive withdrawal reflex, which was less modulated by supraspinal descending inhibitory controls.
In conclusion, much has been discovered and much more needs to be investigated to better understand what causes, how it triggers, keeps and runs out recurrent primary headaches. Clarifying some of these mechanisms might help in the identification of new therapeutic targets. Within the brain, neuropeptides can modulate the strength of synaptic signaling even at a relatively large distance from their site of release.
Given the evidence for CGRP in migraine and potential roles for other hypothalamic peptides, it seems likely that altered neuropeptide actions may be a general theme underlying the heightened sensory state of migraine. Towards this point, I will briefly discuss our preclinical CGRP and optogenetic studies using light aversive behavior in mouse models as a surrogate for migraine-associated photophobia.
I will describe how both the brain and the periphery are susceptible to elevated CGRP and how CGRP appears to act by distinct mechanisms in these sites. These ideas will be tied together in a speculative model that integrates peripheral and central CGRP actions in photophobia.
Classical trigeminal neuralgia TN is a unique neuropathic facial pain disorder. As there are no diagnostic tests to confirm the diagnosis, it relies on a thorough history and exam. MRI is used to exclude symptomatic trigeminal neuralgia, not to confirm the diagnosis of TN. Knowing how to interpret MRI findings is of importance with respect to surgical treatment options and their expected chance of a successful outcome.
TN is characterized by paroxysms of unilateral intense pain usually in the 2 nd and 3 rd trigeminal branch. The pain quality is stabbing and the pain is typically evoked by sensory stimuli like light touch, brushing teeth, cold wind or eating. Up to half of the patients also have concomitant persistent pain.
A smaller proportion of patients may have sporadic autonomic symptoms. The average age of disease onset is in the early fifties and TN is slightly more prevalent in women than in men. As a general rule, the neurological exam is normal in TN patients. As objective signs of TN, patients may wince at pain paroxysms and may avoid shaving or brushing their teeth on the affected side. Some studies argue that a proportion of TN patients have subtle sensory abnormalities at bedside exam, primarily hypoesthesia.
Studies using quantitative sensory testing also documented sensory changes in TN. Rather than indicating nerve damage, the findings may be explained by functional changes of the nervous system in response to severe pain. There is widespread consensus that TN is associated to a neurovascular contact between the trigeminal nerve and a blood vessel in the prepontine course of the nerve.
Emerging advanced imaging studies confirms that at the site of a neurovascular contact on the ipsilateral side of pain, there is of demyelination — a process that seems to be reversible in some patients after successful surgery. Imaging studies also consistently show that TN is strongly associated to a neurovascular contact with morphological changes of the trigeminal nerve, i.
Meanwhile, only half of TN patients have morphological changes of the trigeminal nerve and there may be other unknown etiological factors causing TN. The pearls and pitfalls of TN diagnosis and neuroimaging is discussed from both a clinical and a scientific perspective. The first evidence for potential role of PACAP in pathomechanism of migraine was the intravenous administration of PACAP caused headache and vasodilatation in healthy subjects as well as in migraineurs, and lead to delayed-type migraine-like attacks .
Preclinical experiments revealed that both PACAP and PACAP were found elevated in the trigeminal nucleus caudalis of rats following electrical stimulation of the trigeminal ganglion or chemical stimulation by nitroglycerin of the trigeminovascular system . A magnetic resonance imaging MRI angiographic study demonstrated that PACAPinduced headache was associated with prolonged dilatation of the middle meningeal arteries, but not of the middle cerebral arteries in healthy volunteers .
The recent functional imaging study pointed that intravenous PACAPinduced migraine attacks was associated with alterations in brain network connectivity . Clinical investigation provided evidence of a clear association between migraine phases during a spontaneous migraine attack versus pain-free period and the alteration of plasma PACAP level . The activation and sensitization of the trigeminovascular system by vasoactive neuropeptides might be crucial factors of the migraine pathogenesis .
The recent preclinical and clinical studies suggest the importance of PACAP as a future biomarker of migraine headache. Schytz, H. PACAP38 induces migraine-like attacks in patients with migraine without aura. Tuka, B. Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system. Peptides ; Amin, F.
Cephalalgia ; Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide Brain ; Neurology ; Alterations in PACAPlike immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Several studies are found a relationship between headache and psychiatric comorbidity in both children and adolescents .
The most frequently described comorbidities include anxiety, mood disorders , sleep disorder  and attention hyperactive disorder . The association between headache and comorbidities has been interpreted in the light of different possible causal pathways. Psychiatric comorbidity may represent the consequence of a link between neurotransmitter systems involved in migraine and psychiatric disorder, such as depression and anxiety .
A central role is thought to be played by serotonergic receptors, adrenergic and dopaminergic D2 receptor genotype, that seem to be associated with migraine, major depression, generalized anxiety disorder, panic attacks and phobia . It has been suggested that the patient\’s vulnerability to anxiety disorders and affective disorders as well as migraine might be attributed to the dysregulation of the serotonergic system .
Furthermore, it is possible that each disorder increases the risk of the other [4;7]. Therefore, the relevance of other mediating factors for the co-occurrence of headache and psychiatric comorbidity has to be taken into consideration. Recent research found that an insecure attachment may be a risk factor for an outcome of poor adaptation that includes chronic pain  and that pain perception may change in relation with specific attachment styles.
The ambivalent attachment seems to be the most common style among patients reporting high attack frequency and severe pain intensity and in children with this attachment style there is a relationship between high attack frequency and high anxiety levels . Barone et al. Although more studies are needed in order to detect the biological, genetic and environmental mechanisms underlying the relationship between headache and comorbidities, attachment styles can be regarded as one of the factors mediating this association .
Anxiety, depression and behavioral problems among adolescents with recurrent headache: the Young-HUNT study. The relationship between sleep and headache in children: implications for treatment. Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences. Epilepsy Behav. Migraine and psychiatric comorbidity: a review of clinical findings.
Mol Med. Association of 5-HTT gene polymorphisms with migraine: a systematic review and meta-analysis. J Neurol Sci ; : Headache and comorbidity in children and adolescents. J Headache Pain ; Genetic and environmental influences on migraine: a twin study across six countries.
Twin Res. Pain and emotion: a biopsychological review of recent research. J Clin Psychol ; 67 9 : Attachment styles in children affected by migraine without aura. Neuropsychiatr Dis Treat.
Behavioural problems in children with headache and maternal stress: is children\’s attachment security a protective factor? Dev ; DOI: The role of attachment insecurity in the emergence of anxiety symptoms in children and adolescents with migraine: an empirical study.
J Headache Pain In Press. Metabolic syndrome and overweight are highly prevalent among migraineurs and the weight-loss was suggested as a useful strategy to improve both migraine and metabolic syndrome.
Recently, we have observed that a particular version of VLCD characterized by very low-carbohydrate intake and Ketone bodies KBs production, named very low-calorie ketogenic diet VLCKD , was able to induce a rapid improvement of headache in migraineurs.
To assess if the favorable outcome on migraine was due to the caloric restriction, instead of KBs, we performed a double blind crossover study to compare headache modifications during a VLCD and a VLCKD in a population of overweighed and obese migraineurs. Among patients referred to the Sapienza University Obesity Clinic, a neurologist specializing in headache recruited 35 migraineurs.
To verify variations in headache frequency, we used as baseline the month before the first VLCD and the first transition diet. Headaches are one of the most disabling disorders . Moreover, recent knowledge have suggested that physical examination for provocative procedures should be done on each patient with side- locked headaches as many of these headaches may closely mimic primary headaches .
There have been identified eleven physical tests to properly assess cervical disorders. When these dysfunctions are present, they support a reciprocal interaction between the trigeminal and the cervical systems as a trait symptom in migraine [6, 7].
In this presentation, an evidence based physical protocol of specific tests it will be provided by a physiotherapist to assess musculoskeletal disorders in the most common primary headaches as Migraine and Tension Type Headache.
Moreover, the integration of this examination in a multidisciplinary team it will be discussed. Stovner LJ. Migraine prophylaxis with drugs influencing the renin- angiotensin system. Eur J Neurol. Prevalence of neck pain in migraine and tension-type headache: a population study. Temporomandibular disorders is more prevalent among patients with primary headaches in a tertiary outpatient clinic.
Arq Neuropsiquiatr. Prakash S, Rathore C. Side-locked headache: an algorithm based approach. The Journal of Headache and Pain ; doi International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study. Man Ther. Musculoskeletal dysfunction in migraine patients.
The International Classification of Headache Disorders, 3rd edition beta version Jul;33 9 Headache represents the most common neurological symptom in pediatric age. Among the primary headaches, migraine is far more prevalent than tension-type headache and cluster headache. Though extremely rare at this age, also trigeminal autonomic cephalgias have been reported.
The most frequent causes of pediatric secondary headaches are represented by respiratory tract infections, while potentially life-threatening diseases, such as brain tumors, are less common.
However, especially in the emergency setting, the possibility that a headache attack is due to a brain tumor must be always considered. To avoid missing these cases, some headache characteristics red flags have been identified .
However, while the most recent ICHD criteria improved the possibility to classify some patients, such as children with migraine with aura , they turned out to be unsuitable for others, such as young patients with primary headache.
Several studies have shown the primary role played by psychological factors in determining the severity of migraine in children . Therefore, a psychological examination is often mandatory, as part of the initial assessment of the patient. Lastly, when assessing a child with primary headache, possible comorbidities should be never forgotten, since addressing them can represent a crucial point for the treatment . Headache as an emergency in children and adolescents.
Curr Pain Headache Rep ; Cephalalgia, submitted. Diagnosis of primary headache in children younger than 6 years: A clinical challenge. Cephalalgia ; Chronic Migraine in Children and Adolescents. Headache and comorbidities in childhood and adolescence. Springer, Whether medication-overuse headache MOH represents a distinct biological entity within the concept of chronic daily headache with specific neurobiological and genetic background is still a matter of debate.
A great deal of interest has been directed at understanding the neurophysiological mechanisms that underlie MOH pathogenesis. Currently, two main, non-mutually exclusive hypotheses have been proposed. The first, stems from the apparent compulsive use of headache medications by MOH patients, and considers this disorder a sort of addiction to symptomatic remedies.
The second shifts the focus from drug addiction to neural sensitization, claiming that triptan overuse triggers adaptations of the trigeminovascular system, thereby facilitating pain transmission and leading to a state of latent sensitization. Answering these questions might be relevant to better understand the neurochemical mechanisms prompted by acute headache medications that underlie the pathophysiology of MOH and of chronic headache in general.
In this presentation, preclinical data will be presented showing that chronic exposure to eletriptan or indomethacin alter trigeminal ganglion gene expression patterns broadly and to a similar extend.
Remarkably, qualitative transcriptomic analysis reveals that prolonged exposure to the two different symptomatic drugs triggers almost identical, increased expression of various genes coding for proteins involved in headache pathogenesis such as neuropeptides, their cognate receptors, TRP channels, prostanoid and NO synthesizing enzymes.
These findings will be correlated with the clinical aspects of MOH. The dramatic caloric restriction promotes the fat metabolism, mimicking the starvation, even if meals replacements ad hoc developed accounts for essential nutrients, avoiding the malnutrition. Because of the extreme caloric restriction, this type of diet is very effective in weight loss, however, that characteristic also is the main limit of VLCD, since it is possible to follow this kind of dietetic regimen for a very limited period usually weeks.
Salads are allowed ad libitum dressed with a spoonful of olive oil. Also in this kind of diet, there are meals per day, mainly consisting in meal replacement products. There is a growing interest in the ketogenic form of the VLCD because several studies have shown a higher compliance of patients with this diet.
The reason of this higher adherence to the diet is still under scrutiny but several reasons are called in cause: an appetite suppression induced by proteins and maybe by ketone bodies KBs , or a modification in hormone secretion insulin, glucagon, ghrelin, adipokines. The real impact of ketogenic diets in weight loss is still disputed; in fact, on the long period there are not differences between low-carb and low-fat diets in terms of weight reduction and regain of lost weight after the diet.
However, thanks to the higher compliance and the drastic caloric restriction, the VLCKDs seem to be a promising approach in the early management of obesity and in the preparation phase for patients that must undergo to bariatric or other types of surgical procedures.
Temporomandibular disorders TMD represent the main cause of orofacial pain of non-dental origin and comprehend several disturbances of the masticatory system characterized by myofascial pain of masticatory muscles or articular pain localized in the pre-auricular area. Moreover, TMD patients show temporomandibular joint sounds and deviation or limitation of the opening of the mouth.
Myofascial pain is a probable consequence of central nervous system mechanisms of convergence and activation of second order neurons with enlargement of the receptive field, reduced pain threshold and allodinia.
Often there are accompanying symptoms like facial pain and headaches. Headache is the most prevalent neurologic disorder, third most diffused health disturbance and the seventh cause of disability in the world.
It can be primary, without apparent organic cause, or secondary to other pathologies. Some epidemiological studies indicates that headache is more prevalent in TMD patients and TMD is more prevalent in subjects affected by headache. A stronger association exists between TMD and chronic migraine in comparison with other types of headache.
Nevertheless the methodological quality of the available studies is not optimal and many of them classify patients with anamnestic questionnaire that tend to overestimate the values of prevalence. A growing body of literature suggests that the association between headache and TMD may be a manifestation of a central sensitization mechanism. Temporomandibular joint and muscles receive the sensitive innervation of the trigeminal nerve that supply also the cranial vascular structures likely involved in the etiology of the headache.
The sensitization of the trigeminal caudate nucleus by the TMD symptoms can favor the triggering of migraine episode. Beside the epidemiological studies and the neurophysiologic hypothesis, there are some initial clinical evidence that show how severity of TMD symptoms parallels an increase of frequency and intensity of migraine and the simultaneous treatment of both conditions results in better outcomes.
From a clinical perspective, a comprehensive assessment based on a biopsychosocial approach can provide relevant information to plan a contemporaneous treatment of TMD and headache, together with an intervention targeted to the reduction of psychosocial conditions that can elicit and maintain mechanisms of central sensitization likely responsible of the comorbidity of TMD and headache.
The exact pathophysiology is still unknown, but evidence supporting both peripheral and central mechanisms i. In fact, the frequency of headache attacks has found to be related to the level of central sensitization .
However, not all TTH patients present with the same level of central sensitization and clinical presentation, but subgroups need to be identified in order to offer specific therapeutic programs .
Prolonged peripheral nociceptive input from the pericranial, neck, and shoulder regions e. In fact, it has been found that sustained stimulation of TrPs may induce central sensitization in healthy participants . The number of TrPs seems to be associated with the degree of widespread pressure pain hypersensitivity in TTH patients, supporting the role of TrPs on central sensitization: however the cross-sectional nature of the study does not allow to establish a cause and effect relationship between TrPs and central sensitization, as other variables may influence this association .
Physical therapy may be helpful for the management of TTH patients [10,11], as it may decrese the peripheral nociceptive input. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia ;— Tension type headache. Curr Rheumatol Rev ; — Pressure pain thresholds assessed over temporalis, masseter, and frontalis muscles in healthy individuals, patients with tension- type headache, and those with migraine: A systematic review.
Pain ; — Frequency of headache is related to sensitization: a population study. Pain ; Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia. J Headache Pain ; 18 1 The role of muscles in tension-type headache. Curr Pain Headache Rep. Sustained nociceptive mechanical stimulation of latent myofascial trigger point induces central sensitization in healthy subjects.
J Pain. Myofascial trigger points and sensitization: An updated pain model for tension-type headache. Trigger Points are associated with widespread pressure pain sensitivity in people with tension-type headache. Cephalalgia [Epub ahead of print].
Muscle trigger point therapy in tension-type headache. Expert Rev Neurother ; 12 3 Effectiveneess of physical therapy in patients with tension-type headache: literature review. J Jpn Phys Ther Assoc ; 17 1 Migraine is related to the highest disability among headaches.
Great efforts are faced to improve the outcome of forthcoming treatments. However, still now, many patients regard as unsatisfactory the low responder rate about the half of patients and adverse effects that current treatments account. Therefore, waiting for innovative, more tolerated and effective treatments, there is a large request for non-pharmacological approaches that in many cases have specific pathophysiological targets.
Among these treatments, nutraceuticals has a leading role. Several nutraceutical products are proposed for migraine and sold around the world, but researchers adequately study only few compounds. Among studied nutraceuticals compounds, only few of them have studies of good quality in support. Moreover, also interactions among different molecules are not studied. We have reviewed literature data in order to find researches that support the use of nutraceutical molecules in migraine management.
Available good quality data support the use of certain nutraceuticals, in particular riboflavin, coenzyme Q10, magnesium, butterbur, feverfew, and omega-3 polyunsaturated fatty acids. Even if not supported by double blind studies, recently some prospective observational studies about fixed combination of nutraceuticals were performed.
For instance, it is the case of a combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study. A double blind versus placebo study about the effect of a fixed combination of riboflavin, coenzyme Q10, feverfew, andrographis and magnesium for migraine prophylaxis is currently in progress.
Usually patients appreciate nutraceuticals more than traditional drugs, since they are regarded as safe and of efficacy not inferior to other pharmacological products.
Available data seem to support this widespread belief, but some concerns about the regulation of nutraceuticals and quality of some products, still remain. Contrary to what is generally thought of, headaches and algology pain therapy share many aspects. Headaches and chronic non-oncological pain are two paradigms of chronic illness capable of generating enormous individual and social impact by disabling the sick person not only in the biological, but also in the psychological, professional, social and relational spheres.
Both cause alterations in psychological equilibrium, secondary depression, loss of social and professional roles, which, in the most serious cases, can cause loss of work. Literature documents in both cases, headaches and chronic pain, a rise in direct costs but above all of the indirect ones with a huge burden of disease. Both are capable of generating a marked drop in the quality of life associated with a serious bio-psycho-social disability. Headaches and chronic pain, although distinct according to a topographical criterion, share many mechanisms and physiopathogenetic steps.
One of the most current fields in which neurologists and pain therapists converge is the focus on neuroinflammation  and central sensitization, two key mechanism for triggering, maintaining, and subsequent perpetuation of pain: the pain as a symptom, filogenetically responsible for maintaining homeostasis of the organism against actual or potential damage, becomes unnecessary illness without any protective meaning.
Another important shared pathogenetic passage is that of neuroimmune mechanisms, which interlink the immune system with the central nervous system. Furthermore, numerous contribution to the scientific international literature highlight the need to modify the therapeutic approach, directing it towards a semeiotic criterion pain phenothype: specific sign and symptoms of a certain type of pain in a specific moment , which is an epiphenomenon of underlyng pathogenetic mechanism, instead of basing it on a etiologic criterion.
This would enable a more appropriate prescription and greater efficiency, taking into primary consideration the possibility of getting back to everyday life rather than obtaining complete analgesia. All the above mentioned aspects are equally important but one of them can prevail over the others depending on patient characteristics and background.
In conclusion it can be stated that the aspects of sharing between headaches and chronic non-oncological pain are significantly greater than those that clearly divide them. World Health Organization. International classification of functioning, disability and health ICF. Geneva, World Health Organization, Steiner T. J Lifting the burden: The global campaign against headache. Ru-Rong Ji Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov.
Baron R Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. Headache is a common clinical feature in neurological patients.
Usually, neuroimaging is unnecessary in patients with episodic migraine or tension type headache with typical headache features and with a normal neurological examination. These patients do not have a higher probability of a relevant brain pathology compared to the general population. A recent study, however, reported that neuroimaging is routinely ordered in outpatient headache even if guidelines specifically recommend against their use.
Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all trigeminal autonomic cephalalgias TACs. Neuroimaging should be considered in patients presenting with atypical headache features, a new onset headache, change in previously headache pattern, headache abruptly reaching the peak level, headache changing with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre and abnormal neurological examination.
A recent consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. According the same consensus, fFor primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required . Particularly in emergency room it is mandatory to exclude a secondary headache that requires special attention and further diagnostic workup.
CT scan is the first line neuroimaging examination. MRI offers a greater resolution and discrimination and might therefore be the preferred method of choice in non acute headache. In addition, radiation due to CT scanning may be avoided. Neuroimaging non conventional techniques are of little or no value in the clinical setting. Headache neuroimaging: Routine testing when guidelines recommend against them.
European Headache Federation consensus on technical investigation for primary headachedisorders. Migraine frequency fluctuates over time. In the literature, the most important recognized factors associated to chronic migraine are overuse of acute migraine medication, ineffective acute treatment, obesity, depression, presence of allodynia and stressful life events. Other factors reported in studies are age, female sex and low educational status. Very recently, a large population study suggested that the presence of additional noncephalic pain site is a risk factor for migraine chronification.
For many of these factors the relationship with migraine chronification may however be bi-directional. For instance, in the case of depression, it is possible that depression may negatively affect the response of migraine to acute and prophylactic treatments, but it is also true the opposite: i. In the case of obesity, the association with chronic migraine may simply be ascribed to the effect of fat tissue in drug distribution.
Beside and beyond the putative biological factors that may cause a worsening of disease, several lines of evidence suggest that the progression from episodic to chronic migraine is associated to a progressive increase and stabilization of functional and anatomical changes associated to chronic sensitization.
In this frame, it appears obvious that an additional cause for chronic migraine is quite likely represented by the low rate of prescription of preventive medications.
The underutilization of preventive drugs has several explanations ranging from drug-associated issues limited efficacy, poor tolerability profile to education of practitioners, pharmacists and patients, and it also involve the limited access to qualified care. Underutilization of preventative drugs also translate into a higher recourse to acute drugs, thus feeding on a vicious cycle that leads to negative consequences. CT has participated in advisory boards for Allergan and electroCore; she has lectured at symposia sponsored by Allergan; she is PI or collaborator in clinical trials sponsored by Alder, electroCore, Eli-Lilly and Teva.
Prevalence of migraine sufferers who are candidates for preventive therapy: results from the American migraine study AMPP study. Headache ; — The added value of an electronic monitoring and alerting system in the management of medication-overuse headache: A controlled multicentre study.
To date, the majority of clinical studies concerning primary headaches and their comorbidities are focused on migraine. Comorbidities of migraine may include neurological and psychiatric conditions, as mood disorders depression, mania, anxiety, panic attacks , epilepsy, essential tremor, stroke, and the presence of white matter abnormalities .
Particularly, a complex and bidirectional relation between migraine and stroke has been described, including migraine as a risk factor for cerebral ischemia, migraine caused by cerebral ischemia, migraine mimicking cerebral ischemia, migraine and cerebral ischemia sharing a common cause, and migraine associated with subclinical vascular brain lesions .
A recent meta-analysis pointed out that migraine is associated with increased ischemic stroke risk , and according to a systematic review and meta-analysis  the risk of hemorrhagic stroke in migraineurs is increased with respect to non-migraineurs. Besides, the risk of transient ischemic attack seems to be increased in migraineurs, although this issue has not been extensively investigated .
A recent systematic review and meta-analysis also describes an increased risk of myocardial infarction and angina in migraineurs compared to non-migraineurs . Concerning the association between migraine and vascular risk factors arterial hypertension, diabetes mellitus, dyslipidemia, obesity, alcohol consumption, family history of cardiovascular disease , a recent review  showed no solid evidence of an increased burden of conventional vascular risk factors in migraineurs, with the only exceptions of dyslipidemia and cigarette smoking, while a systematic review and meta-analysis regarding migraine and body mass index categories  found an increased risk of having migraine in underweight subjects and in obese women as compared with normal-weight subjects.
Few studies investigated the comorbidities of tension-type headache TTH , despite the fact that tension-type headache TTH is highly prevalent, and may be as debilitating as migraine . It is noteworthy that, according to a review, TTH is associated with increased rate of affective distress .
Furthermore, some medical disorders may worsen a preexisting TTH, and it has been described the comorbidity of TTH with psychiatric disorders and fibromyalgia . The International Classification of Headache Disorders, 3 rd edition beta version.
Comorbid neuropathologies in migraine. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. Migraine and hemorrhagic stroke: a meta-analysis. Sacco S, Kurth T. Migraine and the risk for stroke and cardiovascular disease. Curr Cardiol Rep. Migraine and risk of ischaemic heart disease: a systematic review and meta-analysis of observational studies. Conventional vascular risk factors: Their role in the association between migraine and cardiovascular diseases. Migraine and body mass index categories: a systematic review and meta-analysis of observational studies.
Tension-type headache and psychiatric comorbidity. Tension-type headache and systemic medical disorders. Differentiating patients with life-threatening headaches from the overwhelming majority with primary headaches eg migraine, tension or cluster headache is an important issue in emergency department ED.
Patients with non-traumatic headaches are up to 4. These numbers seem to remain constant in Western countries Ramirez-Lassepas, ; Kowalski, ; Cvetkovic, ; Gaughran, Primary headaches still pose an open challenge in the ED because the failure to recognize a secondary headache could cause potentially fatal consequences. Unfortunately, to date, there is still no a standard diagnostic procedure for headache in emergency conditions; although according to the diagnostic guidelines there are red flags that could help in the process, the positive predictive value of each severity indicator is not yet determined.
The problem of poor diagnostic sensitivity was attributed to IHCD-3 criteria rigidity in relation to primary headache diagnosis in emergency setting Dutto, , Swadron, Alternatively, a different standardized work-up has been proposed for the most frequent headache scenarios in ED Cortelli, ; Dutto, A careful history and physical examination remain the most important part of the assessment of the headache patient; they enable the clinician to determine whether the patient is at significant risk for a dangerous cause of their symptoms and what additional workup is necessary.
This presentation will discuss how to approach adults with headache in ED with an emphasis on those features that characterize high-risk headaches. Thus, the muscolokeletal contribution in Primary Headaches is still debate in the literature .
Moreover, recent knowledge suggests that different clinical headache phenotypes arising from a common pathophysiology rather than an independent disorder .
That is, in the most prevalent headaches disorders i. In this presentation, the role of the musculoskeletal inputs in primary headaches it will be provided. Moreover, evidences of the effectiveness of a manual therapy management provided by a physiotherapist and its integration in a multidisciplinary team it will be discussed. Migraine prophylaxis with drugs influencing the renin-angiotensin system. The impact of headache in Europe: principal results of the Eurolight project.
Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci. Cady RK. The convergence hypothesis. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain.
Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. The European Headache Federation recognized the value of OnabotulinumtoxinA suggesting that, before labeling a patient as affected by refractory CM, a proper treatment with this drug needs to be completed .
In the last years several real-life prospective studies provided further evidence in clinical setting of OnabotulinumtoxinA U efficacy for the headache prophylaxis in CM complicated by medication overuse headache MOH .
Recently we published the results of a prospective study on the long-term 2 years efficacy and safety of a single dose of OnabotulinumtoxinA or U in patients with CM plus MOH had failed previous preventative drugs and detoxification attempts .
Both the doses were effective and equally safe, but U was more effective than U in reducing headache days, migraine days, pain medication intake days and Headache Impact Test HIT -6 score.