**3. Diagnosis of a migraine**

There is the release of ions, cytokines, and other inflammatory mediators in the environment of sensory fibers that inject the brain envelope. Due to the presence of these substances, prolonged activation of peripheral nociceptors occurs, which is eventually perceived as pain. Neurogenic inflammation prolongs and enhances migraine headaches. Because of inflammation, there is also sensitization [13, 14]. Sensitization of neurons and neural fibers indicates an increase in their susceptibility. The threshold is lowered, and the magnitude of irritability and area of the irritable area grow [12]. Because of this, the weaknesses of the stimuli at perhaps atypical sites can be perceived as pain. Spontaneous neuronal activation also occurs. There are two forms—peripheral and central sensitization. In peripheral sensitization, it is about capturing primary afferent neurons, while in central sensitization, it is more susceptible to "higher" neurons—those in the trigeminal nucleus and other parts of the brain stem and hemisphere. Sensitization is believed to be responsible for many of the clinical symptoms of migraine. Pulsating pain, strengthening pain due to physical activity, hyperalgesia, and allodynia are associated with sensitization.

The association of genetic factors with the onset of a migraine has been first proven in patients with familial hemiplegic migraine (FHM). This is a migraine subtype where an aura appears to be fully reversible motor deficiency [12]. There are three types of family hemiplegic migraines:

• FHM1 is linked to the mutation of the CACNA1A gene, located on chromosome 19p13.1, and encodes for the α1 subunit of the P/Q calcium channel neurons [15]. The P/Q calcium channel manifests multiple expressions in the central nervous system, regulates serotonin and glutamate release in central and peripheral synapses, and is associated with increased susceptibility to cortical widespread depression [16]. With the mutation of this gene, episodic ataxia type 2, paroxysmal disorder causing cerebellar ataxia, migraine-like symp-

• FHM2 occurs due to the mutation of the ATP1A2 gene encoding the α2 subunit of Na/K ATPase. This gene is found on the 1q23 chromosome, and the mutation causes reduced ATPase oligodendrocyte activity and decreased affinity for potassium ions, leading to the reduced removal of the same from the extracellular space and reduction of retention of glutamate from the synaptic cracks [18]. The elevated concentration of potassium ions and glutamate in the extracellular space results in hyperexcitability of the brain [16]. Because of the emergence of isolated FHM, it is also possible to combine with cerebellar symptoms,

• The FHM3 mutation affects the SCN1A gene (on the second chromosome), which encodes the Nav1.1 voltage channel. The Nav1.1 voltage channel is key to generating and spreading neuronal action potential, and genetic mutation causes excessive activation of action potentials and can alleviate cortical widespread depression through several mechanisms: high trigger rates can lead to increased extracellular potassium concentrations and further depolarization and increase the release excitatory neurotransmitter glutamate [15]. In addition to being associated with the emergence of family hemiplegic migraine, this gene is also recognized as a cause of generalized convulsion in adult and childhood epilepsy [16], generalized epilepsy with febrile convulsions, and myoclonic epilepsy in early childhood [20].

childhood convulsions, and the emergence of mental retardation epilepsy [19].

toms, nystagmus, and cerebellar atrophy [17] are associated.

**2.2. Genetics of a migraine**

4 Biofeedback

Diagnosis of a migraine is based on the clinical picture or diagnostic criteria set by the Headache Classification Committee of the International Headache Society [3]. There are two types of a migraine—migraine without aura and migraine with aura. Headaches that occur 15 or more days a month for more than 3 months and 8 or more days of migraine headache are diagnosed with chronic migraine [3].

Specific diagnostic tests for migraine do not exist, and image methods are in most cases not necessary. According to the American Academy of Neurology, the use of radiographic image methods (MSCT, MR) is recommended only if an abnormal neurological status is found and in patients with an atypical clinical history of headaches or headaches that cannot be classified into either a migraine headache or some other primary headache [15]. Differential diagnosis of a migraine without aura includes primarily tensile headache, whereas the differential diagnosis of migraine with aura also involves transitory ischemic attack and partial epileptic seizure. At the setting of diagnosis of a migraine can help presence of auras (the presence of positive phenomena following negative phenomena), the sequence of their occurrence, progression, duration, and possibly the existence of associated symptoms [12].

Also, at diagnostic, it is very important to take an extensive interview to get detailed information on all spheres of life of the person with migraine (frequency, pain, time of occurrence, association with other events, relationship with some period of time, place of appearance of pain and description of pain, susceptibility to events in their own surroundings—greater expectations of oneself or others—sensitivity to criticism, events that could have caused migraines). Being a good listener to hear all the details of the person with migraine is of crucial importance because it also depends on proposing the possible treatment. After an initial interview where we collect all the necessary information, we shall decide together with the person about how to treat a migraine. For biofeedback as a method of treatment, it is very important to find out how much the person is motivated to invest in and separate the time they will devote to these treatments. At some people, it is still a bigger motive to take some medications that will quickly solve their problem.
