Migraine is one of the most common types of headache, which can lead to a significant decrease in quality of life. Researchers identify migraine with aura, migraine without aura, and chronic migraine that substantially reduces the ability of patients to work and is frequently concurrent with mental disorders and drug-induced headache. The complications of migraine include status migrainosus, persistent aura without infarction, migrainous infarction (stroke), and a migraine aura-induced seizure. The diagnosis of migraine is based on complaints, past medical history, objective examination data, and the diagnostic criteria as laid down in the International Classification of Headache Disorders, 3 rd edition. Add-on trials are recommended only in the presence of red flags, such as the symptoms warning about the secondary nature of headache. Migraine treatment is aimed at reducing the frequency and intensity of attacks and the amount of analgesics taken. It includes three main approaches: behavioral therapy, seizure relief therapy, and preventive therapy. Behavioral therapy focuses on lifestyle modification. Nonsteroidal anti-inflammatory drugs, simple and combined analgesics, triptans, and antiemetic drugs for severe nausea or vomiting are recommended for seizure relief. Preventive therapy which includes antidepressants, anticonvulsants, beta-blockers, angiotensin II receptor antagonists, botulinum toxin type A-hemagglutinin complex and monoclonal antibodies to calcitonin gene-related peptide or its receptors, is indicated for frequent or severe migraine attacks and for chronic migraine. Pharmacotherapy is recommended to be combined with non-drug methods that involves cognitive behavioral therapy; progressive muscle relaxation; mindfulness; biofeedback; post-isometric relaxation; acupuncture; therapeutic exercises; greater occipital nerve block; non-invasive high-frequency repetitive transcranial magnetic stimulation; external stimulation of first trigeminal branch; and electrical stimulation of the occipital nerves (neurostimulation).

When examining a patient with lumbosacral pain, it is necessary to rule out the specific cause of the disease. The diagnosis of discogenic lumbosacral radiculopathy (DLSR) is based on clinical examination; magnetic resonance imaging (MRI) is of informative value in excluding other causes of radiculopathy and in evaluating disk herniation. If the signs of cauda equina and spinal cord compression are absent, and no epidural glucocorticoid injection or urgent surgical treatment is scheduled, there is no reason for early (within the first 4 weeks) MRI.
It is recommended to inform the patient with DLSR about the possibility of disk herniation regression and natural recovery and about the advisability of maintaining physical activity. Epidural administration of local anesthetics and glucocorticoids and use of non-steroidal anti-inflammatory drugs are advisable to relieve acute pain. Anticonvulsants (pregabalin and gabapentin), muscle relaxants, and B vitamins can be used as additional methods for acute DLSR; psychological therapies (cognitive behavioral therapy), antidepressants, therapeutic exercises (kinesiotherapy), manual therapy, and acupuncture are effective in chronic DLSR. Consultation with a neurosurgeon for possible microdiscectomy is indicated in the presence of cauda equina syndrome (urgently) and in the absence of medical therapy effects within 4–8 weeks.
Therapeutic exercises (kinesitherapy) with an educational program for prevention of strenuous physical activity and static and uncomfortable positions for a long time, as well as for teaching how to lift weights properly, etc. are recommended for preventive purposes.

To manage patients with drug-induced headache (DIH) is an unsolved problem of modern neurology in developed countries, since DIH is becoming a common cause of temporary disability and leads to lower quality of life in patients. Patients with primary headache (for example, those with tension headache or migraine) frequently take symptomatic headache relief medications uncontrollably, which can result in the higher frequency and intensity of DIH episodes. In turn, new headache attacks make the patients take the increasing number of symptomatic medications, which leads to the development of DIH.
The International Classification of Headache Disorders, 3 rd Edition, defines DIH as a distinct form of secondary headache. To date, there is no consensus on the tactics of DIH treatment and prevention. The paper discusses different approaches to DIH prevention and treatment, the effectiveness and appropriateness of their use, as well as factors influencing illness course and possible outcomes. Particular attention is paid to the management of patients during the withdrawal period, risk factors for DIH recurrences, and ways of their prevention.

Sacroiliac joint (SIJ) dysfunction is a cause of low back pain in 10–30% of cases. In 1993, the International Association for the Study of Pain (IASP) defined the following set of diagnostic criteria necessary to diagnose SIJ dysfunction: 1) the presence of pain in the areas characteristic of SIJ lesions, with special attention to pain in the Fortin area projection, with possible different types of radiation; 2) positive pain provocation tests for a SIJ lesion; 3) reduced pain after intra-articular anesthetic injection; 4) the lack of a specific nature of the lesion (fracture, inflammation, tumor, etc.). Injection of 0.5–2.5 ml of solution of an anesthetic (bupivacaine, lidocaine) and 20–40 mg of triamcinolone or 5 mg of betamethasone (1 ml) into the SIJ area is used as interventional technologies. More prolonged analgesia involves radiofrequency denervation (RFD) of the SIJ, in which needles with electrodes are placed in the projection of the nerves that innervate the SIJ, and their local thermal destruction is performed. The effectiveness of RFD of SIJ requires further investigation.

Traumatic trigeminal neuropathy occupies a special place in the pain continuum. The clarification of genesis and clinical and neurophysiological findings makes it possible to perform differentiation treatment.

Objective: to evaluate the clinical and neurophysiological efficiency of repetitive magnetic stimulation (RMS) and vitamin B complex therapy for traumatic trigeminal neuropathy.

Patients and methods. The investigation enrolled 36 patients (26 women and 10 men) aged 25 to 35 years with inferior alveolar neuropathy following bilateral sagittal split osteotomy. The DN4 questionnaire was used to identify a neurogenic pain component. The intensity of pain syndrome was assessed using a visual analogue scale. A neurophysiological examination involving the recording of brainstem auditory evoked potentials (BAEPs) and trigeminal evoked potentials (TEPs) was made using a Neuro-MEP device (Neurosoft, Russia). Therapy including vitamin B complex was performed in 12 patients. Twenty-four patients received low-frequency pulsed magnetic field therapy using a Neuro-MS magnetic stimulator.

Results and discussion. The clinical picture in patients with traumatic inferior alveolar neuropathy after corrective mandible surgery is characterized by the polymorphism of pain sensations and sensory disorders. The development of pain syndrome is due to a neuropathic component. The 10-day vitamin group B therapy cycle had no substantial impact on the time course of clinical and neurophysiological changes. After the 10-day RMS cycle, there were reductions in swelling and the intensity of pain syndrome and the severity of sensory disorders in the lower lip, chin, and mandible. The data on BAEPs showed shortening in the interpeak intervals III–V; those on TEPs demonstrated a decrease in the P1–N1 amplitude.

Conclusion. Unlike vitamin B complex therapy, the RMS cycle in patients with traumatic trigeminal neuropathy makes it possible to reduce the intensity of pain syndrome and the severity of sensory disorders, as well as excitability of the nonspecific structures of the brainstem and the central structures of the trigeminal system.

Objective: to investigate the efficacy and safety of citicoline (Ceresil^® Canon) in patients with post-stroke cognitive impairment.

Patients and methods. Examinations were made in 33 patients aged 45 years and older who had experienced primary ischemic hemispheric stroke with complaints of a decline in memory or other cognitive functions. The cognitive status was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The presence of anxiety-depressive spectrum disorders was determined on the Hospital Anxiety and Depression Scale. All the patients received citicoline (Ceresil^® Canon) oral solution at a dose of 1000 mg/day for 3 months.

Results and discussion. Citicoline administration showed a statistically significant reduction in the severity of cognitive impairment (p<0.001). The time course of positive changes in the cognitive status of patients was reflected by an increase in the median score on the MMSE from 26 [25; 27.5] to 28 [26.5; 29] and on MoCA from 23 [21; 25] to 25 [22; 26]. There was a decline in the number of patients with anxiety-depressive disorders. No adverse events or side effects were found in the patients.

Conclusion. The findings suggest that citicoline (Ceresil^® Canon) produced as an oral solution is well tolerated and improves cognitive functions and affective sphere in patients in the recovery period of ischemic stroke.

Depression is a common comorbid diagnosis in patients with eating disorders (EDs). The development of pathogenetic therapy for depression with EDs is far from being completed.

The objective of the psychopharmacotherapeutic study was to evaluate the efficacy and tolerability of melatonergic monotherapy with the antidepressant agomelatine (25–50 mg/day at night) for depressions with two ED variants: hyperphagic (n=32) and hypo- and aphagic (n=31) EDs.

Patients and methods. The investigation enrolled patients of both sexes, aged 18 to 65 years. The investigators performed clinical psychopathological and experimental psychological studies, as well as psychometric examination using the 21-item Hamilton Depression Rating Scale (HDRS-21), the Clinical Global Impression (CGI), the Supplemental Hospital Offset Payment Program (SHOPP), the Dutch Eating Behavior Questionnaire (DEBQ), and statistical data processing.

Results and discussion. There was a significant pronounced antidepressant effect of 6-week agomelatine therapy for depressions occurring with different ED variants both in the pattern of the depressive symptom complex and in that of concurrent with and preceding the latter. At the same time, the efficacy of the drug did not depend on the clinical presentations of the leading hypothymic syndrome, the variants of EDs, and the duration of actual depression. However, by the end of the study period, a larger effect was achieved in the therapy for depressions with the hyperphagic variant of EDs, as well as in patients with EDs manifesting in the pattern of depressive symptom complex. Agomelatine has a favorable tolerance profile. BMI tends to become normal in patients with different variants of EDs during the therapy. The adverse events are transient and/or unclear; they do not require therapy discontinuation.

Conclusion. Agomelatine is an effective and relatively safe drug that can be recommended to treat depressions concurrent with EDs in therapeutic dosages for at least 6 weeks.

Objective: to investigate the clinical and diagnostic characteristics of patients with low back pain in the presence of sacroiliac joint (SIJ) disease.

Patients and methods. The investigation design involved three visits: V 1 (inclusion); V 2 (after 7 days), and V 3 (after 3 months); after the screening period, the investigation enrolled 259 patients aged 65.5 [62.5; 69.5] years; of them there were 165 (63.7%) women. At V 1 , according to magnetic resonance imaging findings, the patients were divided into two groups: 1) 157 patients without confirmed SIJ disease; 2) 102 patients with confirmed SIJ disease. During all visits, the investigators made general clinical and neurological examinations and assessed the intensity of pain syndrome according to a visual analogue scale (VAS) for pain in millimeters, a neuropathic pain component according to the DN4 questionnaire, by determining the blood parameters: transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), IL-6, Beta-Crosslaps, the indicator of bone matrix formation procollagen type 1 N-terminal propeptide (P1NP) and by estimating the urinary level of deoxypyridinoline.

Results and discussion. At all visits, Group 2 patients with higher VAS pain scores had a pain history that was statistically significantly longer (p<0.001). The ANOVA analysis showed that the patients in Group 2 had statistically significantly higher values of TGF-β1, IL-1β, IL-6, and bone resorption markers than those in Group 1, which suggests the relationship between pain syndrome and the presence of an inflammatoryresorptive process in patients with SIJ disease.

Conclusion. A high (39.4%) prevalence of SIJ disease was noted in patients over 60 years of age with low back pain. During the follow-up period, there was a decrease in bone resorption markers and cytokines; however, the SIJ disease group showed less pronounced changes with statistically significant differences in all parameters than in the non-SIJ disease group. It is advisable to consider an algorithm for diagnosing a patient over 60 years of age with low back pain, by mandatorily examining his/her SIJ. Treatment policy, including methods for correction with drugs, should be discussed based on the findings.

Three clinical cases of the syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) are first described in Russian literature. The patients were young (aged 30–35 years), had symptoms characteristic of the prodromal period of infections. In all the patients, the disease started with intense headache, followed by focal neurological symptoms: aphasia and hemihypesthesia in all cases and confusion with psychomotor agitation in two cases. All the three patients showed spontaneous recovery within 2–3 days. Perfusion computed tomography, magnetic resonance imaging, and electroencephalography are compared in one of the cases. The differential diagnosis of HaNDL with acute cerebrovascular accident, herpetic encephalitis, epilepsy, and migraine is discussed.

The paper deals with the actual problem of managing patients with drug-induced headache (DIH) in patients with primary headaches. It describes a clinical case of extremely severe DIH in a patient with chronic tension headache (TH). The paper analyzes the typical and atypical manifestations of DIH and discusses the role of prolonged stress in the development of TH. Special attention is paid to the problems with therapy and compliance during a long-term follow-up of the patient. Based on the clinical features of pain syndrome in the described patient, the authors suggest for the first time that the use of extremely high number of daily doses of combined narcotic analgesics for many years can result in recurrent DIH statuses. The paper discusses whether it is expedient to introduce the concept “DIH severity” and whether an additional clinical parameter “the number of doses of painkillers per month” can be of informative value, which has not been proposed yet in the literature. All the issues given in the paper are conjectural and are raised by the authors for further investigation of the DIH problem.

Cubital tunnel syndrome (CTS) is the second most common compression mononeuropathy that is effectively treated. The risk factors for CTS include repetitive arm flexion at the elbow joint and prolonged arm flexion with support on the elbow. The diagnosis of CTS is based on its clinical presentations, the data of neurological examinations, and the results of electroneuromyography and ultrasound examination. The symptoms of the disease progress quickly, therefore the early diagnosis of CTS and its timely treatment are of great importance for the patient's recovery. Unfortunately, patients with CTS are often observed to be erroneously diagnosed with degenerative and dystrophic spinal changes. The paper presents an observation of effective treatment in a young patient who has been suffering from CTS for a long time and been erroneously diagnosed with spinal osteochondrosis. Six months after surgical treatment (for decompression and neurolysis of the left ulnar nerve), the patient regained hand sensitivity and movement. It is concluded that further investigation is necessary to assess predictors of effective surgical treatment in patients with this disease.

Objective: to investigate the effect of dexketoprofen on the severity of seizures on a rat model of primary generalized seizures caused by thiosemicarbazide; to evaluate the neuroprotective effect of the drug.

Material and methods. The investigation was conducted on 72 male albino rats weighing 200–300 g. The animals were given dexketoprofen and/or comparison drugs (gabapentin, sodium valproate) for 5 days, after which the seizure model was reproduced. The effects of the drugs were evaluated from a set of neurological tests and the results of a histopathological examination of the brain.

Results and discussion. Dexketoprofen reduced the severity, duration, and number of primary generalized seizures and potentiated the anticonvulsant effects of gabapentin and sodium valproate. Histopathological and morphometric examinations of the rat brain showed that dexketoprofen inhibited the formation of irreversible neuronal changes (27.2%; control, 55.7%), by transferring them into reversible changes (47.7%; control, 21.8%).

Conclusion. The investigation made it possible to conclude that dexketoprofen had a moderate neuroprotective effect neurologically and morphometrically verified.

Objective: to investigate the effect of citicoline (CTC) on gene transcription.

Material and methods. Chemotranscriptome analysis of the CTC molecule was carried out on an NPC.TAK model, provided that the cells were incubated with CTC for 24 hours.

Results and discussion. CTC dose-dependently affected the transcription of 8,838 out of 12,716 annotated human genes, mainly by increasing the transcription of the genes involved: 1) in the neurotransmitter metabolism of serotonin (n=36), dopamine (n=32), GABA (n=14), and acetylcholine (n=27); 2) in showing the effects of neurotrophic factors (n=152), including nerve growth factor (n=11); 3) in maintaining the cardiovascular system (vasodilation and cardiac electrical activity; a total of 76 genes). CTC reduced the transcription of the genes, whose protein activity supported inflammation (n=86) and cell division (n=656). CTC elevated the expression of 60 genes involved in triglyceride processing and decreased the expression of 51 genes whose proteins were involved in cholesterol metabolism. CTC increased the transcription of the genes involved in the body’s response to various drugs, including antiepileptic drugs (n=20), dopaminergic agents (n=19), antipsychotics (n=38), anxiolytics (n=21), sedatives (n=22), antidepressants (n=35), anesthetics (n=23), and antidementia drugs (n=11).

Conclusion. Chemotranscriptome analysis indicated the positive effect of CTC on neurotransmission, neuroprotection, lipid profile, and a higher neuronal susceptibility to other neuroactive drugs.

The relationship between cognitive impairment (CI) and depression is complicated: h\the latter can be one of the symptoms of Alzheimer’s disease or may precede the onset of CI. Depression also has cognitive symptoms that alter the clinical presentation of the disease. Patients with depressive pseudodementia experience difficulties concentrating, confusion concurrent with impaired memory and thinking, whereas the patient’s answers to certain questions often resemble the vague pseudoamnestic pattern of the impairment. Mnestic disorders occur in at least 40% of patients with depression, and if the latter is diagnosed in the patient who already has dementia, the rate of cognitive decline may be faster. The mechanisms underlying the development of CI can also affect the development of depression. When assessing the risk of dementia in depression, it is necessary to take into account the time from the onset of a major depressive episode until moderate CI appears, to carry out a detailed analysis of neuropsychological testing for Alzheimer’s disease and to use the current lifetime markers for amyloidosis and neurodegeneration. Serotonergic antidepressants and non-pharmacological cognitive behavioral and psychotherapeutic procedures play the most important role in the treatment of depression and dementia.

Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

The most common form of peripheral nervous system damage in diabetes mellitus is distal symmetric sensorimotor polyneuropathy (DSSMPN). Chronic hyperglycemia, dyslipidemia, and impaired microcirculation are considered to be the key mechanisms for the development of DSSMPN, but its pathogenesis is still unclear and continues to be studied. The paper analyzes the issues of diagnosis of DSSMPN and the effective principles of patient treatment. It also discusses the use of alpha-lipoic acid (ALA) as a drug for the pathogenetic treatment of DSSMPN and describes the results of clinical trials of its treatment with ALA preparations.

To manage patients with chronic back pain (CBP) is one of the urgent problems of modern medicine, as CBP is associated with high disability, considerable socioeconomic costs, and low quality of life. Concurrent disorders, such as insomnia, depression, and anxiety, which make a significant contribution to the severity of CBP and related disability, are frequently disregarded when managing patients with CBP. Insomnia is observed in the majority of patients with CBP, but it is relatively rarely diagnosed, therefore the bulk of patients do not receive appropriate treatment. Cognitive behavioral therapy (CBT) combined with therapeutic exercises is one of the most effective treatments in patients with CBP; moreover, of great importance is the identification of concomitant insomnia, whose treatment with CBT is able not only to improve sleep, but also to reduce pain and to increase the physical and social activities of patients. A positive combination treatment effect is achieved due to a change in the patients’ ideas about the prognosis and causes of the disease, as well as to the increased intensity of physical activity and to the prevention of strenuous exercise and static stresses.

The review provides historical information on the medical use of cannabinoids from antiquity to the present day. It presents the most common indications for their use in neurology, oncology, and psychiatry for the treatment of social diseases, such as epilepsy, pain syndromes, spasticity, including multiple sclerosis, Parkinson's disease, depression, schizophrenia, dementia, etc. There are data of the largest-scale and evidence-based studies using cannabinoids to treat epilepsy. The paper depicts the main mechanisms of action of these drugs and gives information about their efficacy and safety, as well as possible adverse events. Limitations and legal aspects are discussed. Systematic reviews and meta-analyses show that today there have been sufficient positive study results worldwide, indicating the validity of the medical use of cannabinoids. At the same time, experimental and clinical studies are needed to further investigate the mechanisms of action of cannabinoids, the characteristics of their pharmacokinetics and pharmacodynamics, efficacy and safety for many severe and disabling diseases.

To manage patients with vascular cognitive impairment (VCI) is an extremely difficult task, since drug therapy algorithms have not been elaborated, whereas the prescription of most drugs has not always been pathogenetically justified. Today, both our country and foreign countries have no uniform standards for VCI treatment, and the choice of drugs in everyday clinical practice is largely determined by a physician’s personal experience. The paper discusses main areas in the drug treatment of VCI and provides a detailed analysis of studies evaluating the efficacy and safety of basic drugs used to correct cognitive deficit. The basic anti-dementia medications (akatinol memantine and acetylcholinesterase inhibitors) recommended as mandatory treatment have been identified. The remaining groups of drugs are proposed to be used in combination therapy as add-on treatment, by taking into account individual indications. It is concluded that add-on investigations are needed to select the treatment algorithm differentiated preferably for different clinical and pathogenic VCI variants, which should also consider not only the features of clinical manifestations, but also the magnitude of structural and functional changes in the cerebral vessels and brain matter.

Nonspecific back pain (NBP) is one of the most common reasons to see a neurologist or therapist. Acute (<4 weeks' duration), subacute (4 to 12 weeks), and chronic (>12 weeks) NBPs are recognized. The diagnosis of NBP is based on anamnestic data, somatic, neurological, and neurologic-and-orthopedic examination findings and on the exclusion of the specific causes of back pain, discogenic radiculopathy, and vertebral canal stenosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants are used in the pharmacotherapy of acute, subacute, and chronic NBP. Tolperisone is widely used as a muscle relaxant in Russia and in the countries of Europe and Asia. Clinical trials have shown the efficacy and good tolerance of tolperisone used alone and in combination with NSAIDs for NBP. The review presents clinical recommendations from different countries on the use of muscle relaxants in the treatment of acute and chronic NBP. It is concluded that a large-scale qualitative randomized trial should be conducted to investigate the efficacy of muscle relaxants, tolperisone in particular, in the treatment of acute, subacute, and chronic NBP.

Migraine is a common chronic neurological disease. Many neurogenic, vascular, autonomic, and other mechanisms at different levels of the central and peripheral nervous systems are assumed to be implicated in the pathophysiology of headache and other manifestations of migraine. Advances in understanding the neurobiology of migraine have made it possible to clarify the main patterns of neurogenic-vascular relationships that explain the leading clinical manifestations of migraine, as well as to identify some biological markers that have triggered the creation of new targeted therapies for the disease. This review is dedicated to the latest advances in studying the pathophysiology of migraine and to new pharmacological approaches to its treatment.