Headache: the most common cases, Some aspects of therapy

Associate Professor, dept. of Neurology and Neurosurgery, BelMAPO, Ph.D.,

Sadokha K.A.

 One of the most common cases of pain and patients’ complaints, as well as the reasons for emergency care is HA (Headache). According to various epidemiological studies, HA is observed in 80% of European working population. However, not all the patients appear on doctors screen as they prefer self-medication. Nevertheless, when HA episodes increase in frequency or intensity interfering with a normal life style and work, the patient makes an appointment to see a doctor, while having a long experience of unsystematic self-administration of various painkillers. HA diagnosis, on the one hand, involves the exclusion of HA symptomatic nature and on the other hand, it requires its specific form determination. In accordance with the modern principles of the International Classification of Headache Disorders, 3rd Edition (ICHD-3), there are two main group forms of HAs: primary and secondary. Primary HAs are much more common and make up to 95-98% of all forms of headache. The diagnosis of primary form HA suggests that medical history, objective and neurological examination, additional research methods do not reveal structural damage to the brain, other organs and systems, i.e. exclude the symptomatic nature of HA. Secondary forms of headache include HA manifested in diseases of known etiology: trauma, damage to the head, neck, cranial, cervical vascular disorders, non-vascular intracranial processes, prolonged medication or overdose, infectious diseases, impaired homeostasis, damage to the skull, neck, eyes, ear, nose (paranasal sinuses), teeth and oral cavity, as well as other facial and cervical structures, mental disorders (two types: HA in somatized mental disorders and mental illnesses).

Headache of Tension (HAT) is considered the most common form of primary HA. The disease starts at any age. The prevalence of HAT during in a general population lifespan according to various studies varies from 30 to 78%. On average, the age-related onset of HAT is 20-30 years with the peak incidence occurred in 20-39 yrs. HAT ratio of men and women is 4:5. Diagnosis is based on the following clinical features: 1) usually HA of bilateral localization, compressing or constricting, often in a form of “bend” or a “helmet”; many patients describe the pain as “encircling around the temples”; 2) pain syndrome of mild or moderate intensity, usually not accompanied with nausea and vomiting, but at the same time appetite may decrease up to anorexia; sometimes mild sensitivity to light or sounds may occur; 3) in some patients, HA can be more pronounced on one side of the body, but usually it is bilateral and diffused; 4) most patients during HAT episode retain the ability to work and perform their usual duties; 5) pain can appear shortly after waking up and may present throughout the day, then intensify, then weaken; often HAT attack begins in the afternoon after hard work; 6) pain occurrence or intensification in emotional experience, anxiety, stress and its relief with positive emotions (in rest, pleasant events) can be considered as characteristic signs of HAT; sometimes even switching attention (for example, a desired meeting, telephone conversation, watching a movie) can ease the pain.

International Criteria for HAT diagnosis is based on the following: I) HA lasting from 30 minutes to 7 days with at least 2 symptoms: 1) bilateral localization; 2) compressing/constricting HA (pulsating is not characteristic); 3) the pain is not increased in normal physical activity; 4) mild/moderate intensity (can reduce work efficiency without its limitation); II) both of characteristics: 1) no nausea or vomiting (no/or reduced appetite); 2) only one of the following symptoms: sensitivity to light or sounds; III) the primary HA.

Additional diagnostic signs of HAT: 1) “bend” or “helmet” pain pattern; 2) mild/moderate intensity (up to 6 points on a visual analogue scale – VAS); 3) pain relief in positive emotions, switched activity; 4) increased pain in emotional experience.

In ICD-10 into par G44.2 is included: Headache of Tension (chronic, episodic). In the current classification of hypertension subtypes of episodic pain are divided into rare (less often than once a month) and frequent (once a month or more frequently) seizures. In chronic HAT pain lasts for more than 15 days per month (over 180 days per year). The above mentioned subtypes are further divided into two categories depending on the presence or absence of pericranial muscular tension. HAT is a disease with no precursors, vomiting and focal neurological disorders. Moderate and low intensity pain in HAT is observed in 87-99% of patients. Pain, as a rule (in 90% of cases), is symmetrical. Patients with HAT often associate pain episodes with stress, post-physical activity and mental tension. An emotional factor is one of the most important in the origin of HAT. For episodic HAT the cause is transient emotional experience: conflicts at work, quarrel with loved ones, anxiety about the child, unsuccessfully done important assignment and any other unexpected troubles. In cases where a conflict or a stressful situation continue for a long time period (more than 2-3 weeks), there is a danger that rare episodes of HAT will begin to repeat more and more often, until the daily headache. This situation leads to a chronic form of HAT with constant compressive pain, feeling constriction around the head which turns into a serious problem. For both episodic and chronic forms of HAT muscle tension plays an important role. Due to the cervical muscular-tonic syndrome, the majority of patients with HAT, along with a headache, complain of transient or constant pain or feeling tension and discomfort in the back of the head, back of the neck and shoulder girdle (“coat hanger” syndrome), as well as facial muscles, more often chewing and temporal muscles.

Muscle tension often occurs in postural tension, the condition associated with a prolonged uncomfortable position of the neck and head, in prolonged work at a computer, driving, gardening, after a dental appointment, etc. Repeated muscle tension leads to over excitation of spinal neurons, increased sensitivity of muscle pain receptors, postural disorders and increased pain. Mandatory for patients with HAT (especially in a chronic form) emotional stress and mental disorders (depression and anxiety) also support muscle tension, contributing to the pain increase. Muscle-tonic syndrome (MTS) can be detected by palpation of pericranial muscles. HAT without tension in pericranial muscles is characterized by zero or an increased electromyographic activity in these muscles. This type of HAT was formerly called “psychalgia,” although the psychogenic factor can trigger the onset and/or intensification of any type of headache. Thus, in a great majority of patients the diagnosis of HAT is made on the patients’ complaints (the characteristic pain pattern) and the medical history (the connection of pain episodes with negative emotions, chronic stress and prolonged postural tension). In many patients the detailed questioning reveals complaints of increased anxiety, bad mood, melancholy, apathy or conversely, aggression and irritability, bad night sleep pattern. MTS (muscle-tonic syndrome) is observed with severe pain in the pericranial muscles up to the “jump symptom” (due to muscle pain the patient actively refuses palpation) in two or more muscle groups. In additional electrophysiological and neuroimaging methods of examination organic changes are not detected in these patients.

For all patients with HAT the basic principle of treatment is combination of two approaches: headache episodes relief and preventive therapy. Preventive therapy is prescribed to a greater extent in patients with chronic HAT. In patients with domination of pericranial muscles tension observed in clinical examination the treatment should start with physiotherapy, massage, blockade with anesthetics and relaxing procedures. For current pain alleviation it is preferable to use non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are among the most commonly used in medical practice. It is well known that NSAIDs are used by more than 80% of doctors of various specialties. The comparative analysis of NSAIDs one dose effect has been conducted and evaluated in more than ten randomized clinical trials. It should be noted that an increased risk of cardiovascular complications in case of high dose has been proven for all drugs except Naproxen. It is important to note that of all over-the-counter drugs, Ibuprofen and Naproxen did not demonstrate any risk at lower doses. Naproxen was not associated with an increased risk when used at high doses (550 mg BID), while Ibuprofen was dose dependent. Among NSAIDs Naproxen is one of the safest drugs for the cardiovascular system due to its stable suppression of platelet aggregation, thromboxane synthesis. Naproxen safety at high doses (550 mg BID) in respect to the risk of atherothrombosis has been proven – the risk does not increase. The world scientific community considers Naproxen as the drug of choice in patients with cardiovascular risks. Naproxen in a form of sodium salt is an active component of the drug Naproff-Reb. This ensures quick and complete absorption of the drug after oral administration. Due to its sodium salt, Naproff-Reb possesses a significant analgesic effect in 15 min. after administration. Because of the long half-life (12-15 hours), only two doses of Naproff-Reb per day are sufficient. If necessary, the specialist is able to control the pain within 24 hours period. For prophylactic treatment of HAT and episodic pain relief Naproff-Reb at a dose of 1000 mg QD demonstrates the necessary spectrum of significant therapeutic (analgesic and anti-inflammatory) activity in combination with the highest cardiovascular safety profile among all NSAIDs. This combined effect makes it possible to consider Naproff-Reb as an ideal prospect and an alternative to the existing therapeutic agents to treat inflammation and pain, various forms of headache, including pain episodes caused by HAT.

There are data that prove the importance of targeted diagnosis and treatment of muscle-tonic syndrome manifestations in patients with HAT. HAT episode provokes spastic pain in pericranial muscles. The vicious circle is formed: pain – muscle tension – pain. Noting the importance of MTS in pathogenesis and chronicity of HAT, muscle spasm therapy should be one of the important goals in treatment of this disease. In this aspect, muscle relaxants that interrupt this vicious cycle are relevant. They are prescribed in combination with NSAIDs, as they enhance their effect and significantly reduce the need for NSAIDs. In most clinical guidelines around the world muscle relaxants are used as a part of a multidisciplinary exposure to enhance the effect. Recently, one group of muscle relaxants has been given preference to drugs with a central mechanism of action to relieve muscle spasm by spinal connections blockade with inhibition of their reaction by suprasegmental centers. One of these muscle relaxants is Reblaks. Its active substance is Thiocolchicoside, obtained from natural glycoside Colchicoside, which exhibits selective activity to gamma-aminobutyric acid and glycine receptors. This ensures its action at various levels of nervous system in muscle spasms of central and peripheral origin. It is assumed that gamma-aminobutyric acid receptors activation occurs in the spinal cord and leads to striated muscles relaxation. Glycinomimetic effects are demonstrated at the level of the brain and the spinal cord. Thiocolchicoside possesses muscle relaxant, anti-inflammatory, analgesic and anesthetic effect and is very often used in clinical practice. Reblaks with the active substance thiocolchicoside is quite often used in patients with HAT. It was demonstrated that treatment with Reblaks at a dose of 8 mg per day in combination and monotherapy results in a more significant decrease in severity of muscle-tonic and pain syndromes of various genesis. Reblaks does not possess a curare-like effect, does not cause paralysis and does not affect the cardiovascular and respiratory systems. High efficiency and safety of this drug makes it highly recommended to be used by medical practitioners for treatment of HAT (Headache of Tension).

The second most common cause of headache is migraine, which has been known from high Antiquity. Even in the ancient Egyptian papyri written more than 3000 years ago, the clinic symptoms of migraine seizures had been described together with drugs prescriptions given to treat this disease. At least one third of humanity has been suffered from migraines in one millennium time period. Women suffer 2-3 times more often than men. The characteristic sign of migraine is its occurrence at the young age, up to 20 yrs. The specific feature of this disease is its periodic stereotypical attacks of throbbing pain, usually one-sided, more often in the orbital or frontotemporal region, accompanied with nausea, sometimes vomiting, poor tolerance to bright light, loud noises, drowsiness, lethargy after the attack. The recurrence of seizures and hereditary predisposition are characteristic. Clinically, the attack occurs in several phases: prodromal, aura, headache accompanied with symptoms and postdromal. Symptoms in the prodromal period occur before the migraine attack and continue from several hours to 2 days. More common prodromal symptoms include irritability, physical and mental hyperactivity, increased sensitivity to light, sounds, irresistible food preferences, increased bowel and bladder function, thirst, feeling of distraction, lethargy, tiredness, difficulty of eyes focusing, yawning, or excessive drowsiness, blurred speech, impaired concentration, general weakness, anorexia. At the end of prodromal period an aura or pain phase starts. Gradual pain increased from mild to moderate and then intense form is characteristic. In most cases the pain is one-sided. Nevertheless, the side of pain can change even during one attack. The pain occurs in an inner eye area, the postorbital or frontotemporal zone, initially dull then it may become thumping (intensified with each pulse beat). Migraine pain in most cases is characterized by considerable intensity, lasts from 4 to 72 hours. There is a historical evidence of significant intensity of migraine pain. An unknown ancient poet lived about six thousand years ago described his classic migraine headache. The fragments of a clay tablet with his poem discovered by archaeologists upset historians. The decrypted cuneiform writing did not reveal anything new. The poet sang not the beauty of the landscape, not the feats of arms, not the life of Kings and Gods but described his headache in detail. Half of his head was cracked with pain, the poor fellow ceased to see, so that he was not interested in surrounding beauties. Modern doctors diagnosed the forefather with a migraine (Megapolis Express. 1996, No. 20). There are ancient legends about migraine. Even the omnipotent Zeus – the ruler of the ancient Greek Gods, according to an ancient legend, had to turn to Hephaestus, the God of blacksmithing, so that he would smash his head cracking from unbearable pain with a hammer and save him from monstrous migraine attack. There is also a literary example that indicates a significant intensity migraine attack. Mikhail Bulgakov who had medical education, in his famous novel “The Master and Margarita” gave the precise description of “a terrible, invincible disease – hemicrania, when half a head hurts.” The procurator of Judea, Pontius Pilate, caught in a migraine attack, saw the salvation in a portion of poison only. Over the millennia mankind has invented other ways to relieve pain but the symptoms of this disease remained the same. Many patients in the pain phase experience a variety of accompanying symptoms in a form of hypersensitivity to bright light, loud noise and various smells. As the migraine attack subsides, many patients experience a postdromal period when they experience difficulty in concentration fixation, weakness, depression, loss of energy, impaired coordination and drowsiness. Post-attack period continue from several hours to 2 days. Migraine attacks vary tremendously in severity, timing and severity of accompanying symptoms in different patients and also vary in one patient but in different attacks. Migraine is divided into two main forms: migraine without aura (MWA) and migraine with aura (MA). MWA is observed in 80% of all cases. MA is much less common and observed in about 5-10% of all patients with migraine. Aura is a disorder manifested in recurring episodes of reversible focal neurological symptoms that increase within 5-20 minutes period and lasts for not longer than 60 minutes. Most frequently occurred types of aura (visual, sensory and speech) are defined as typical forms of aura. Visual disturbances are the most common aura symptoms that occur in 99% of patients with MA, at least in most attacks. Sensitive aura type is observed in 30-54% of patients with MA, speech aura form – in 20-32% of patients. Thus, visual aura type is observed in almost all attacks, speech and sensory – only in some attacks. The most typical manifestation of visual aura is a flickering scotoma when an image periodically disappears in some parts of the visual field and flickering sensation appears with luminous objects on the blind area periphery. Symptoms of flickering scotoma in different people can be observed in different ways. Usually it begins with a small blind spot in the center of visual field, then it increases and moves. In addition, the patient can see lightning and flickering in the blind spot. Some patients note that at the time of migraine attack they can see castles in the air and other amusive objects. Typically, these symptoms last for 20-30 minutes, sometimes the blind spot disappears much faster. Rare types of aura include olfactory, auditory, motor, aura in a form of systemic dizziness, as well as an aura with neuropsychic functions violation. Differential diagnosis takes into account the following migraine characteristic signs: 1) stereotypical attacks of pulsating unilateral headache in the temple, forehead, parietal, less often in the occipital region; alternation of the pain side from attack to attack; 2) seizures offset in childhood, puberty or youth; 3) typical accompanying symptoms: nausea and/or vomiting, hypersensitivity to light, sound, smell, increased pain in normal physical activity (for example, when walking, climbing stairs); 4) typical provoking factors: stress, changes in weather, hunger, excessive or insufficient sleep, alcohol (red wine, beer, champagne), stuffiness and periods; 5) hereditary pattern (in 60% of patients); 6) no seizures in the third and fourth pregnancy trimesters.

Migraine treatment is guided by the following basic principles: 1) paroxysms frequency depending – attacks alleviation or prevention; 2) periodic course of antihypoxants, antioxidants, taken into account the important role of hypoxia and oxidative stress in disease pathogenesis. Traditionally, the treatment of seizures can be roughly divided into non-specific and specific. Nonspecific therapy involves drugs that are used to treat pain in different area. Our ancient colleagues, just like all of us today, have always wondered: how to relieve the painful migraine attack. A piece of canvas with the Gods names on it was used as a tight bandage on the head for pain alleviation, as the disease was considered as “punishment from the Heaven”. In fact, facilitating effect was most likely associated with scalp compression and vasoconstriction. Shakespeare offered the similar recipe: to relieve Othello’s headache, Desdemona bandaged his head with his handkerchief. Scientists have noticed this effect, so all specific anti-migraine drugs are vasoconstrictors. Thus, pharmacological agents prescribed to stop the migraine attack are divided into groups: 1) drugs with a non-specific mechanism of action: a) analgesics (acetaminophen, codeine); b) non-steroidal anti-inflammatory drugs (acetylsalicylic acid, dexketoprofen, naproxen, ibuprofen, diclofenac, etc.); c) combined (cofergot, cofetamine, syncapton, solpadein and others); 2) specific anti-migraine agents: a) triptans – selective agonists (stimulants) of serotonin receptors (sumatriptan, zolmitriptan, naratriptan, etc.); b) non-selective agonists of serotonin receptors (ergotamine preparations); 3) adjunct treatment (metoclopramide, domperidone, etc.). The specific drug selection is based on individual characteristics, such as the headache pain intensity, the rate of its increase, associated symptoms, maladaptation degree, previous treatment experience and patient preferences. It is recommended to use pain relievers at the same time or better in 20 minutes after antiemetics (metoclopramide – tablets or suppositories 10-30 mg; levomepromazine – 10-50 mg orally or i/m – 12.5-25 mg; domperidone – tablets 20-30 mg or suppositories 30-60 mg), promotility agents which accelerate stomach emptying and analgesics absorption at the time of headache attack.

Non-steroidal anti-inflammatory drugs traditionally hold a significant position in treatment and prevention of most pain syndromes. The strategy for a migraine attack therapy is based on an effective and fast-acting NSAID selection. Effectiveness in migraine attacks treatment and prevention has been reliably confirmed with the use of Naproxen, especially its sodium salt (Naproff-Reb). The drug is rapidly and completely absorbed after oral administration. Due to its sodium salt, in 15 min. after Naproff-Reb intake it demonstrates significant analgesic effect, well tolerated and also has a predictable pharmacokinetic profile, available without prescription which is very important for the migraine attack therapy. This is one of the safest drugs among NSAIDs (with min risk of cardiovascular events). In case of migraine attack therapy Naproff-Reb can be used as an alternative to the parenteral drug form, in emergency and under inpatient treatment. Migraine attack duration is an equally important factor used to assess the drugs adequacy when applied in patients for headache therapy (Amelin A.V., 2007). It is known that therapeutic active plasma concentration of ibuprofen persists for 5-6 hours; for naproxen – it is up to 18 hours (min). This fact should be taken into account when choosing the drug for pain relief in a migraine attack lasting for more than 6 hours. In such situations the first-line drug is Naproff-Reb. Otherwise, to stop the migraine attack completely it would be necessary to take analgesics or NSAIDs again, which in turn will increase the spectrum of all known side effects, especially for the gastrointestinal tract (GIT). According to results of Vitebsk Regional Diagnostic Center (the center for paroxysmal conditions, non-curable headache therapy cabinet), it is not recommended to take analginum, paracetamol, diclofenac in moderate and severe pain syndromes, since their effectiveness, as a rule, is insufficient (Naumova G.I., Prusakova O. I., 2013). Ibuprofen effect is best to check during one seizure and in a greater dose (800 mg) but if the patient initially suffers from seizures accompanied by severe nausea or vomiting, the drug effectiveness is unlikely. Thus, in severe pain phase of migraine attacks, vegetative manifestations (nausea, vomiting) lasting more than 6 hours, the first-line drug is Naproff-Reb. In case of true menstrual migraine (migraine attacks occur exclusively in the perimenstrual window (PMW) and do not occur at other cycle periods) or in migraine attack associated with the menstrual cycle, seizures are usually more severe. In attempt to make attacks easier, if the patient has no problems with the gastrointestinal tract, experts recommend to try the mini-prophylaxis method at least 3 times in a row. Naproxen is used (2 tablets per day, 550 mg each) within 2-3 days before the expected first day of menstruation and then for 5 days period.

According to literary sources data, the probability of migraine attack which may never occur is about 15-20%, but the attacks will definitely be mild in severity with less limited social activity. In this case, as a rule, it is no need to use in addition other analgesics. Moreover, it was shown that in a long-term follow-up period such mini-prophylaxis decreased probability of headache progression to a chronic or drug (abusive) form (Latysheva N.V., Filatova E.G., 2012). Currently, in double-blind, placebo-controlled studies among all drugs known for short-term migraine prophylaxis only Naproxen 1100 mg dose per day has been shown to be effective (Tabeeva G.R., Yakhno N.N., 2011).

An important advantage of NSAIDs is the availability of parenteral drug forms aimed to achieve quick pain relief effect, including the migraine pain. The prominent representative of “urgent” NSAIDs is Rebofen® (dexketoprofen) – solution for intravenous and intramuscular administration (concentrate for solution for infusion preparation 50 mg/2 ml No.10). The mechanism of double analgesic effect of Rebofen is based on pain substances synthesis inhibition, cyclooxygenase activity (COX) decrease at peripheral and central level. Due to its high lipophilicity, the drug very well penetrates through the blood-brain barrier. Its highly expressed activity against COX at two levels determines high analgesic and anti-inflammatory effects. For quick relief of high intensity pain parenteral administration of Rebofen^® at a dose of 50 mg in 8-12 hours interval is advisable. If necessary, the repeated dose should be taken in 6 hours. The total daily dose should not exceed 150 mg.

In everyday clinical practice, prophylactic treatment of migraine is used extremely rare. At the same time, it has been proved that the success of migraine therapy is largely determined by early and active prevention of migraine attacks. Summarized data on drugs recommended by The European Federation of Neurological Societies (EFNS) experts for prevention of migraine attacks based on analysis of the series of placebo-controlled study results are mentioned below. Second-line therapy drugs can be useful when no effect observed with first-line drugs therapy or contraindications presented, as well as in a number of comorbid conditions. The first-line therapy drugs, according to the EFNS recommendations: 1) beta-blockers (metoprolol (50-200 mg); propranolol (40-120 mg); 2) calcium channel blockers (flunarizine 5-10 mg); 3) anticonvulsants (valproic acid preparations – 500 mg); topiramate (25-100mg). Second-line therapy drugs: antidepressants, naproxen, bisoprolol.

Based on important role of hypoxia and oxidative stress in migraine pathogenesis, periodic treatment course with antihypoxants and antioxidants are recommended in accordance with the generally accepted scheme. Carnitines could be of particular interest in this regard. Brain tissue is rich in carnitine, and its concentration is quite high in various parts of the central nervous system, characterized by different functional activity (in hypothalamus, cerebellum, cortex, spinal cord, etc.) in comparison with its low content in some other tissues and blood plasma. There are two isomers of carnitine – right - and levoisomer (D- and L-forms), which possess different chemical and biological features. It is considered that in a human and animal body there is L-carnitine (levocarnitine) which is biologically active and also safe to use. In The Republic of Belarus CARNIMET (Levocarnitine) is registered. L-carnitine is involved in mitochondrial oxidation of fatty acids – the main source of energy, especially in physical activity.

Therapy with this drug results in increase in Carnitine content in tissues, restores loss of Carnitine, reduces symptoms severity and its manifestations in ischemia, which is important for various forms of headache. L-carnitine (Carnimet) administration in clinical practice is characterized by an increased interest and various aspects of its effect on biochemical processes in the body have been studied. The data accumulated have proved that various effects of L-carnitine cannot be explained only by the effect on energy metabolism. Over past ten years its ability to reduce free radicals damaging effect to the cell and its organelles has been studied in detail which explains quite high protective effect on a number of diseases associated with headache of different origin. It has been demonstrated that the protective effect of Carnimet is realized by increased synthesis of anti-inflammatory and antioxidant molecules. The experimental data on protective effect of L-carnitine to organelles, primarily mitochondria is not limited by suppression of lipid peroxidation processes. L-carnitine administration leads to an increase in activity of the cell’s own antioxidant enzymes. Nitric oxide penetration into large vessels results in normalization of endothelial function. Carnitine protective effect on the brain tissue in ischemia-hypoxia can be mediated by the decrease in damaging effect of excitatory amino acids, in particular glutamate. Glutamate capturing mechanisms provided by neurons in acute ischemia is an important process for the nerve cells survival rate increase. The preliminary course of Carnimet therapy was accompanied by greater functional preservation of the brain, confirmed by higher cognitive functions indicators demonstrated in relevant studies. The data obtained enabled to register significant improvement of abstract and concrete thinking, memory on the top of already administered therapy. An increase in acetylcholine concentration – one of the key neurotransmitters in cognitive functions implementation, mainly in the frontal cortex and hippocampus was observed and in quantity significantly exceeded the corresponding parameters in the control group. There is an evidence of L-carnitine metabolite – acetyl-L-carnitine participation in acetylcholine synthesis in the brain. The data available on acetyl-L-carnitine positive effect in patients with cognitive impairment suggest the possibility of positive effect when L-carnitine prescribed to patients with pre-dementia form of disease. An exceptional interest to L-carnitine is based on ability to prevent apoptosis, activate various mechanisms that control the processes of delayed cell death. Carnitine intake reduces the severity of tissue hypoxia, improves the level of microcirculation and energy metabolism. Carnimet (5 ampoules by 5 ml – 200 mg/ml in a pack) is administered intravenously 1-2 times a day. The optimal daily dose is 1000 mg. The complete course of treatment is 10-20 injections. In addition to dripping model of injection, it is possible to perform slow bolus injections (within 2-3 minutes) of the drug product. In a number of studies it has been demonstrated that repeated treatment course of Carnitine after 2-3 months period is quite advisable. However, it should be noted that both regimens: daily dose and the course of treatment can be increased depending on the patient’s condition, neurological deficit severity and treatment efficacy. Most authors consider various possible mechanisms of Carnimet efficacy. There is an evidence that energy metabolism correction and suppression of lipids peroxidation processes, as well as elimination of excitatory amino acids damaging effects, inflammatory substances along with the blood flow restoration can reduce the area of ischemia, the severity of pain syndromes in different localization and neurological deficit. Thus, experimental and clinical data available today indicate a rather high efficiency of Carnimet in various central nervous system diseases accompanied with headache of different, especially vascular, origin.

Unfortunately, migraine drug therapy may not be enough and therefore non-medication therapy of migraine in the attack-free period is recommended (mountain climate therapy, acupuncture, percutaneous electro-neurostimulation, hypnosis, relaxation techniques of behavioral psychotherapy, their combination with biological feedback, electromyographic biological feedback, autogenic training, treatment with light lamps – phototherapy, dosed hypobaric hypoxia, ozone therapy, etc.). In case of pericranial muscles tension post-isometric relaxation, soft manual therapy, collar zone massage and reflexotherapy are recommended.

Traditionally migraine is considered to be a favorable condition for prognosis. Meanwhile, it is a chronic disease, usually able to destroy the normal lifestyle, affects work performance and family relationship. In most cases migraine attacks occur spontaneously and unpredictable. This condition is associated with the feeling of fear, apprehension and, accordingly, disturbs the daily life. That is why migraine is included into the List of 19 chronic diseases (WHO) that to the greatest extent violate patients’ social adaptation. At the same time, many people believe that migraine – one - half of the head disease – is the fate of great people due to their brilliant thoughts. It is worth to remind ourselves that many extraordinary people suffered from migraines, including famous politicians – Julius Caesar (migraine and epilepsy), Napoleon I, Karl Marx; famous composers – Ludwig van Beethoven, Richard Wagner, Frederic Chopin, Peter Tchaikovsky; writers – Anton Chekhov, Mikhail Bulgakov, Heinrich Heine, Virginia Woolf, Edgar Allan Poe, Guy de Maupassant; scientists – Isaac Newton, Jean Calvin, Carl von Linne, Blaise Pascal, Charles Darwin, Alfred Nobel, Friedrich Nietzsche, Sigmund Freud, Jean Martin Charcot; artists – Pablo Picasso and others.

Headache is a modern medical and social problem. According to the most recent WHO systematic review explaining the development and causes of diseases, injuries and risk factors for health (Global Burden of Disease Survey), headache and migraine are recognized as the second and the third disease in the world in terms of prevalence rate in the population (Salomon JA et al., 2012). Migraine ranked seventh among 289 specific causes of disability in developed countries and was the leader among neurological diseases reduced working performance (Vos T. et al., 2012). The relevance and important medical and social significance initiated a large-scale experimental-clinical study of the most common causes of headaches. In clinical, neurophysiological and neuropharmacological aspects the problem of headache continues and is now being actively developed worldwide, being studied in many laboratories, research centers, foreign institutes and in our country. This Article summarizes and systematizes information available in the world literature about headache, its most frequent causes, criteria for timely diagnosis, adequate methods of treatment, which should be useful for neurologists, therapists and other specialists. The prevalence, common diagnostic problems and mistakes, economic cost and significant decrease in quality of life determine the most important aspect of headache and practical significance of this publication.