Background. Memory and attention deficits are prevalent in the chronic pain population. There are multiple common mechanisms in chronic pain and cognitive impairment. However, the presence, prevalence and clinical burden of such impairment are frequently underestimated.

Objective: to evaluate subjective and objective cognitive deficits in patients with chronic migraine (CM).

Materials and methods. We recruited 53 subjects with CM and 22 genderand age-matched controls with low-frequency episodic migraine (a maximum of 4 headache days per month) aged 18–59. All patients filled in the HADS (Hospital Anxiety and Depression Scale) anxiety and depression scale and Pittsburg Sleep Quality Inventory (PSQI). Cognitive function was assessed with Montreal Cognitive Assessment (MoCA), Digital Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT) and the Perceived Deficits Questionnaire (PDQ-20).

Results. 56 % of patients with CM complained of memory problems. Decreased cognitive function was also observed during self-assessment using the PDQ-20 questionnaire. Objectively, we found a significant decrease in 90-second DSST results and RAVLT total recall and learning rates. 44 % of subjects with CM scored lower than 26 points on MoCA. Most frequently we found impairments in attention (75 %), memory/delayed recall (50 %), language (50 %) and executive function (37 %). Depression and sleep quality correlated with only several parameters of cognitive tests.

Conclusion. Subjective and objective cognitive deficits are prevalent in the CM population. Most often memory and attention are impaired. Cognitive complaints need to be carefully assessed, and treatment of such impairment may improve quality of life and decrease disability in CM.

The article is devoted to the unexplored period of life of the famous Russian neurologist and psychiatrist of the first half of the 20th century Mikhail Sergeyevich Dobrokhotov (1878–1952). Based on the first time archived materials brought into scientific circulation from the funds of the State Archives of the Rostov Region, the Central State Archives of the Republic of Dagestan, the archive of the Dagestan State Medical University, the milestones of the life path of the privat-docent M.S. Dobrokhotov in the city of Rostov-on-Don, where he lived and worked during the Civil War. The authors consider the multifaceted activity of M.S. Dobrokhotov in the Don University. For the period of the Civil War, the most difficult years occur in the history of the medical faculty, at the department of psychoneurology of which the university professor M.S. Dobrokhotov. The authors focus on the functioning of the health care system of the Don region in the period under review. A separate place is given to the history of the department and the clinic of psycho-neurology of the University, since after the First World War the number of patients with psycho-neurological disorders increased sharply. In addition, on the basis of archival materials, the history of the Don Traumatology Institute is being reconstructed, the director of which was M.S. Dobrokhotov. It was in this institution that the combatants were provided with specialized medical care: the treatment of fractures, contractures, paralysis, neuroses, and lesions of the central and peripheral nervous system. The article reveals the history of the creation of the Rostov Society of Doctors-Psycho-Neurologists, whose members were famous Russian scientists A.I. Yushchenko, S.N. Davidenkov, K.S. Agadzhanyants, V.V. Brailovsky, N.M. Itsenko, N.M. Krol’ and others. A certain place is also given to M.S. Dobrokhotov in the post of head of the psychiatric section of the Don Regional Department of Health.

Background. Arthrogryposis is one of the most severe congenital abnormalities of the musculoskeletal system characterized by 2 or more contractures of the large joints, muscle and anterior grey column pathology. One of the main problems making selfcare limited or impossible for the patients is an absence of the active movements in the joints of the upper extremities which can be restored through autologous transplantation from the various donor areas. Processes of the rehabilitation after these operations are associated with neuronal remodeling in the central nervous system both in the spinal cord and the brain, in the cortial regions in particular.

The objective is to evaluate possible reflection of arthrogryposis in the amplitude and neurodynamical characteristics of the electroencephalogram (EEG) in children.

Materials and methods. Electrophysiological characteristics of the cerebral cortex in children with arthrogryposis and healthy children of the same age were examined. Such EEG characteristics as power and long-range temporal correlations (evaluation of the neuronal activity dynamics) in ranges of 4–8, 8–12, and 12–16 Hz were measured. The results were evaluated in accordance with clinical scales.

Results. Data analysis has shown that children with arthrogryposis have significantly decreased EEG power in all of the studied ranges compared to healthy children. Additionally, a significant correlation between EEG power and the level of restoration of motor functions in the upper extremities after autologous transplantation of various muscle groups in the position of the biceps was observed. The obtained results reflect correlation between the electrophysiological parameters of the cerebral cortex and processes associated with arthrogryposis pathology. However, neurodynamical parameters in children with arthrogryposis are similar to those in healthy children. The results allow to state that arthrogryposis is reflected through decreased electrical activity of the cerebral cortex in 4–16 Hz range with preservation of neurodynamic characteristics typical for disease-free children.

Conclusion. In this study, a significant difference in EEG power in 4–8, 8–12, and 12–16 Hz ranges between children with arthrogryposis and healthy children was demonstrated. However, there was no difference in such an important neurodynamical characteristic as longrange temporal correlations. It is possible that decreased amplitude of EEG rhythms in children with arthrogryposis is caused by their lower motor activity in general.

Background. Hexanucleotide repeat expansion in the C9orf72 gene is the most significant cause of a large number of neurodegenerative diseases: frontotemporal degeneration (FTD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), etc. Several studies have shown the relationship with the neurodegenerative process for full (>40 GGGGCC copies) and intermediate (13–20) repeats expansion. Methylation of the C9orf72 gene can play an important role in the pathogenesis of FTD and ALS, but the mechanism has not been sufficiently studied.

The objective is to investigate the status of methylation of the 5’-promotor region of the C9orf72 gene in patients with neurodegenerative disorders having full or intermediate expansion of GGGGCC-repeats.

Materials and methods. We investigated the methylation status of the 5’-promoter region of full C9orf72 expansions in FTD/ALS patients (n = 12), of intermediate expansions in Parkinson’s disease patients (n = 8) and of non-expanded alleles in healthy controls (n = 8). Methylation status was determined via sequencing of amplified fragments of bisulfite-converted DNA.

Results. We identified two cases (sibling) with the hypermethylation of the 5’-promoter region in the full C9orf72 expansions group. Patient A. (65 years old, male) had an atypical ALS presentation: an onset with head tremor, a long duration of ALS symptoms (9 years at this time), and cognitive impairments with a temporal lobes atrophy. The patient’s sister had a similar clinical phenotype. There were no cases of the promoter hypermethylation in the intermediate and control groups.

Conclusion. This is the first data on the 5’-promoter region C9orf72 gene methylation in Russian population. The frequency of the promoter methylation in this group was 9.1 % that consistent with previous studies in other populations. Atypical clinical presentation may indicate a modifying effect of methylation in this area on the ALS phenotype.

Background. A large number of single gene disorders with seizures in clinical picture has been described. Among them, a special place is held by early-onset epileptic encephalopathies (EEE) – a genetically diverse group of disorders characterized by manifestation of seizures in the first 2 years of life and severe progressing course. Currently, 58 genetic variants of EEE has been identified.

The objective is to analyze the incidence, clinical and genetic characteristic of type II EEE in a sample of patients from Russia identified by whole exome sequencing using next generation sequencing.

Materials and methods. The patient sample included 67 children (35 boys and 32 girls) with ages varying from 4 months to 10 years. All patients underwent neurological examination using the standard techniques. Monitoring of electroencephalography (EEG) was performed in accordance with the International 10–20 system. For magnetic resonance imaging, tomographs with magnetic induction of 1.5 and 3.0 T were used. The identified changes were confirmed by Sanger sequencing using DNA from the patients and their parents.

Results. In total, 67 patients with EEE were diagnosed, 8 of which had causational mutations in the SCN2A gene: p.Leu1611Pro (c.4832T>C), p.Cys728* (c.2184C>A), p.Arg607* (c.1819C>T), p.Val1325Ile (c.623T>C), p.Leu419Met (c.1255T>A), p.Asp1487Glu (c.4461C>A), p.Val208Ala (c.3973G>A), p.Gln1211Lys (c.3631G>A). Analysis of parent DNA had shown that all mutations appeared de novo. At the time of disease onset, all patients had multiregional epileptiform activity per EEG. Focal seizures, myoclonic seizures, and epileptic spasms were the most common types of seizures in the patients. The majority of patients (5/8) had diffuse muscular hypotonia. All patients had pronounced mental deficiency. All patients received more than 2 therapy regimens (including hormonal therapy and ketogenic diet) but full remission wasn’t obtained. In some patients, partial positive dynamic was registered with hormonal therapy and sodium channel blockers. Various mutations in the SCN2A gene caused a similar clinical picture but had different functional significance which determined the effectiveness of anti-epileptic therapy.

Background. Unlike parameters of phrenic nerve conduction in healthy adults characterized by stability, in children variations with age are observed. The objective is to investigate the M-wave latency and amplitude in electroneurographic (ENG) examination of the phrenic nerve in healthy children of different ages for development of a normative database of neurophysiological data.

Materials and methods. 48 healthy children (28 girls and 20 boys) were examined. Mean age was 9.19 ± 5.43 years (1–18 years). ENG examination of the phrenic nerve was performed with the modified standard procedure of stimulation at the level of the outer margin of the lower third of the sternocleidomastoid muscle with registration of M-wave from standard diaphragm point and parallel registration of the muscle activity from m.deltoideus and m.serratus anterior.

Results. Mean values of the M-response latency were 5.64 ± 1.25 ms, amplitude – 0.66 ± 0.34 mV. For age-differentiated subgroups 1–2 years (n = 7), 3–5 years (n = 9), 6–12 years (n = 15), and 13–18 years (n = 17), the latency was 4.96 ± 1.94; 5.01 ± 1.13; 5.42 ± 0.84, and 6.44 ± 1.43 ms, respectively; the amplitude was 1.01 ± 0.37; 0.87 ± 0.31; 0.61 ± 0.24, and 0.45 ± 0.21 mV, respectively. The M-response amplitude values in children aged 1–2 years significantly differed from the values in children aged 6–12 and 13–18 years.

Conclusion. ENG examination of the phrenic nerve is a technically uncomplicated procedure, and the obtained data is easy to interpret. During phrenic nerve ENG in children, it is necessary to take age variability of the M-wave latency and amplitude into account. The M-wave amplitude in healthy toddlers (1–2 years old) was significantly lower than in children aged 6–18 years.

Background. Spinal muscle atrophies (SMA) are a group of diverse heterogenous diseases caused by mutations in several dozens of genes. A rare form of autosomal dominant SMA predominantly affects muscles of the lower extremities.

The study objective is to describe clinical and genetic characteristics of Russia-living patients with SMA predominantly affecting muscles of the lower extremities caused by the DYNC1H1 gene mutation discovered by next-generation exome sequencing.

Materials and methods. To diagnose the syndrome a complex of examination techniques was used: genealogical analysis, neurological examination, electromyography, and DNA diagnostics. Changes in the nucleotide sequence in the probands and their parents identified with massive parallel sequencing were studied using direct automatic sequencing with oligonucleotide primers.

Results. Five (5) patients from 4 families with heterozygous mutations in the DYNC1H1 gene were identified. In the patients, one type of SMA predominantly affecting the lower extremities was assumed. Prior to exome sequencing, all patients were monitored for myelodysplasia diagnosis, and magnetic resonance imaging of the spine has showed protrusions and/or spondylolisthesis of the lumbar spine in 4 of the patients. The obtained results can demonstrate both hyperdiagnosis and that spinal pathology is one of the characteristic symptoms of SMA predominantly affecting the lower extremities.

Conclusion. The obtained results allow to make an assumption about a wide range of clinical polymorphisms in patients with mutations of the DYNC1H1 gene. Apart from typical clinical manifestations of SMA predominantly affecting the lower extremities, patients can be diagnosed with hereditary motor and sensory neuropathy 2, myelodysplasia, and congenital arthrogryposis which has to be taken into account during diagnostic search.

This prospective clinical and sonographic observation of the 29 y.o. woman with acute neuropathic pain along the course of the radial nerve, who was later diagnosed with hourglass-like focal radial nerve constriction at the level of the inner fold of the elbow. Dynamic observation was carried out at the level of the most severe pain (at the inner fold of the elbow), starting from the 3rd day after onset of symptoms and within 15 months. At the time of patient’s admission pain syndrome and paresis of extensor muscles of the hand and fingers were significantly pronounced, but we didn’t detect any sonographic changes of the radial nerve. During dynamic observation the segment of focal peripheral nerve constriction has been detected on the 30th day of observation and the portion of multisegmental constriction on the 57th day of observation, but the observed changes did not correlate with the rate of neurologic deficit restoration. On the scans of the radial nerve obtained 9 and 15 months after disease onset the uniform decrease in the nerve diameter was evident, which made it impossible to visualize focal peripheral nerve constriction.

Background. Hereditary motor and sensory neuropathies (HMSN) are a genetically diverse group of disorders of the peripheral nerves characterized by gradual development of weakness, muscular hypo-/atrophy, sensory disturbances in distal areas of the extremities. Currently among the recessive forms, the most prevalent HMSN is associated with the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene (GDAP1-HMSN).

The objective is to present an observation of a family case of HMSN type IVA with unusual genealogy.

Materials and methods. Clinical, electrophysiological, and genetic characteristics of a Russian family with GDAP1-HMSN were examined.

Results. We describe a family with autosomal recessive HMSN and unusual genealogy due to homozygous and compound heterozygous mutations of GDAP1.

Conclusion. The particularity of the described family case is the unusual genealogy with the patients in two non-consecutive generations. This type of inheritance is caused by presence of mutations in compound heterozygous state in the proband's grandson which was confirmed by genetic analysis. The presented case demonstrates the importance and necessity of full analysis of the GDAP1 gene or identification of 2 mutations in trans-position in the proband and subsequent assessment of possible risks for future generations. Multiple stroke-like episodes in the 2 affected members of the family are described that have not been previously reported for GDAP1-HMSN. Stroke has been presented in HMSN associated with mitofusin-2 gene which also as GDAP1, affects mitochondrial function in the neurons.