[Plasma and salivary acetylcholinesterase activity in amyotrophic lateral sclerosis]. / Aktivnost' atsetilkholinesterazy krovi i slyuny pri bokovom amiotroficheskom skleroze.

OBJECTIVE: Assessment of plasma and salivary acetylcholinesterase (AChE) activity in patients with amyotrophic lateral sclerosis (ALS) and in an animal model of the disease. MATERIAL AND METHODS: We studied 41 participants, aged 31 to 71 years, including 17 patients with diagnosed ALS (ALS group, average age 62.3±2.2), 9 patients with ALS mimics (disease control, average age 58.1±2.9), and 15 healthy people (normal control, average age 57.7±2.3). Plasma and salivary AChE activity was measured by using the Ellman colorimetric method. ALS severity was assessed using the ALSFRS-R scale. The King's College staging system and the Milano-Torino Scale (MiToS) were used to determine the stage of the disease. Transgenic FUS-mice were used as ALS model. RESULTS: Plasma AChE activity in the ALS group did not significantly differ from the control groups. There was also no significant correlation between plasma AChE activity and disease parameters such as the stage, duration, rate of progression, and severity. In transgenic FUS-mice plasma AChE activity also did not differ from wild-type mice. However, it has been shown that patients with ALS have significantly higher saliva AChE activity compared to normal controls. However, patients with the bulbar form of ALS had significantly higher values of salivary AChE activity compared to healthy controls. CONCLUSION: In patients with the bulbar form of ALS, an increase in salivary AChE activity was noted, which can be used for diagnostic and prognostic purposes. There is no significant change in plasma AChE activity in ALS patients.

[Treatment of cognitive, behavioral and mental disorders in patients with vascular dementia: results of a multicenter, randomized, double-blind, placebo-controlled clinical trial]. / Lechenie kognitivnykh, povedencheskikh i psikhicheskikh narushenii u patsientov s sosudistoi dementsiei: rezul'taty mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya.

OBJECTIVE: Evaluation of the efficacy and safety of Prospect in the treatment of cognitive, behavioral and mental disorders in patients with vascular dementia (VSD). MATERIAL AND METHODS: In a double-blind, placebo-controlled, parallel-group randomised clinical trial, 406 patients aged 60-85 years old with a diagnosis of mild/moderate vascular dementia (10-24 on the Mini-Mental State Examination (MMSE)) and without signs of depression (Cornell Scale for Depression in Dementia (CSDD) scores ≤10) were included. At Visit 1, complaints and medical history were collected, vital signs were recorded, cognitive impairment was assessed using MMSE and MoCA, NPI-C and CSDD were completed, and an MRI brain scan was performed. Patients were randomised into two groups: patients in group 1 received Prospekta in a dosage of 2 tablets two times a day for 24 weeks, and patients in group 2 received Placebo according to the study drug regimen. RESULTS: Patients in both groups had no differences in demographic and baseline clinical characteristics. Administration of Prospekta for 24 weeks reduced cognitive impairment in patients with vascular dementia compared to the placebo group. The mean MoCA score increased from 17.0±3.6 [17.1±3.6] to 20.5±4.7 [20.4±4.7] in patients treated with Prospekta, whereas it increased from 17.3±3.7 [17.3±3.8] to 19.2±4.9 [19.2±5.0] in the Placebo group. Treatment with the medication also reduced the severity of neuropsychiatric symptoms as measured by the NPI-C scale. The mean score on this scale decreased from 57.0±26.7 [56.7±25.4] to 39.8±23.6 [39.8±23.5] in the Prospekta group and from 55.5±25.5 [55.3±24.4] to 42.8±27.6 [42.3±25.3] in the Placebo group. The difference in mean MoCA and NPI-C scores between the Prospekta and Placebo groups was statistically significant. CONCLUSION: Prospekta is an effective and safe drug for treating cognitive, behavioural and mental disturbances in patients with vascular dementia.

[Clinical significance of subthreshold cerebellar tonsil ectopia into foramen magnum and Chiari malformation type 0]. / Klinicheskaya znachimost' podporogovykh ektopii mindalin mozzhechka v bol'shoe zatylochnoe otverstie i mal'formatsiya Kiari nulevogo tipa.

Cerebellar tonsil dislocation into foramen magnum exceeding 5 mm is traditionally considered as Chiari malformation type 1. This disease requires surgical treatment in case of severe clinical manifestations. In patients with hypoplasia of posterior cranial fossa (PCF), subthreshold tonsil dislocations or tonsil position inside the foramen magnum can result clinical signs identical to Chiari malformation type 1. These disorders are presumably referred to phenotypic variant of Chiari malformation type 1 (Chiari malformation type 0). The authors discuss the data on the prevalence and mechanisms of cerebellar tonsil ectopia into foramen magnum, the role of hereditary and environmental factors in development of PCF hypoplasia and its role in Chiari malformation type 1 and 0. Significance of MR-based morphometry of PCF in identifying the primary forms (Chiari malformation type 1 and 0), clinical and radiological signs of malformation type 0, as well as data on surgical treatment of Chiari malformation type 0 combined and non-combined with syringomyelia are analyzed. Literature data confirm validity of the concept of Chiari malformation type 0. We emphasize the need for further analysis of this problem to identify sensitive and specific diagnostic signs of Chiari malformation type 0 and determine optimal treatment strategy.

[Biomarkers of amyotrophic lateral sclerosis]. / Biomarkery bokovogo amiotroficheskogo skleroza.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that has no effective treatment. To date, ALS is considered as a multifactorial heterogeneous disease, in which the death of motor neurons is a final result of the different pathological pathways. Modern diagnostic criteria and classification of ALS do not take into account all heterogeneity of the disease. Despite the development of molecular neurobiology and neurophysiology, genetics, and technology, significant progress in understanding the pathogenesis of ALS, the disease is diagnosed primarily on the basis of clinical manifestations. In recent years, a number of clinical trials of promising drugs have failed to show positive results. Among the reasons for these failures are variability of ALS forms, patients enrollment already at a late stage of the disease, the lack of use of biomarkers for patients selection and drugs' pharmacodynamics assessment. The study of biomarkers and their implementation in clinical practice can help to solve these problems. Here we will discuss the fluid-based biomarkers for ALS.

[Dislocations of the cerebellar tonsils in the large occipital foramen and the spectrum of Chiari malformations Type 1]. / Dislokatsii mindalin mozzhechka v bol'shoe zatylochnoe otverstie i spektr mal'formatsii Kiari 1-go tipa.

A review on the pathogenesis, clinical picture and diagnosis of dislocations of the cerebellar tonsils in the large occipital foramen and the spectrum of Chiari malformations Type 1 is provided. The issues of surgical treatment of such patients are discussed.

[Therapy of moderate cognitive impairment in the early recovery period of ischemic stroke]. / Terapiya umerennykh kognitivnykh rasstroistv v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

OBJECTIVE: To assess the efficacy and safety of prospecta in the treatment of moderate cognitive impairment in the early recovery period of ischemic stroke. MATERIAL AND METHODS: The study included 275 patients (mean age 64.0±8.1 years) with a history of single ischemic stroke from 3 to 6 months, with moderate cognitive impairment, and moderate activity in everyday life, who were randomized in two groups. During the screening phase, the severity of cognitive impairment was assessed with the Mini-Mental State Examination and Montreal Cognitive Assessment scales; the level of activity in everyday life was evaluated with the Barthel Scale; and quality of life was assessed with the Stroke Specific Quality of Life Scale. Patients took 2 tablets of prospecta or placebo 2 times a day for 24 weeks. The follow-up period was 4 weeks. The primary endpoint of the study was the proportion of patients with improvement in cognitive function (+1 or more on the MoCA test) after 24 weeks of treatment. The occurrence and type of adverse events (AEs), their severity, relationship to the drug, outcome, changes in vital signs, and the proportion of patients with clinically significant abnormality in laboratory tests were analyzed to assess the safety. RESULTS: A clinically significant improvement in cognitive function was obtained in 91.9% of patients in the prospecta group vs 82.,1% in the placebo group, (p=0.02). There were 57 AEs in 37 (27.4%) Prospecta group patients and 53 AEs in 39 (27.9%) Placebo group participants (p=1.00). No AEs were certainly associated with taking the medication. No clinically significant changes in vital signs or abnormal laboratory results were detected during the study. CONCLUSION: Prospecta is an effective and safe treatment option for patients with moderate cognitive impairment in the early recovery period of ischemic stroke.

[Clinical and radiological rationale for distinguishing subtypes of primary Chiari I malformation]. / Kliniko-radiologicheskoe obosnovanie vydeleniya podtipov pervichnoi mal'formatsii Kiari 1-go tipa.

OBJECTIVE: To clarify a role of distinct factors that form the morphological basis of the classical or primary Chiari type 1 malformation (CM1) in the development of its clinical manifestations and subtypes. MATERIAL AND METHODS: The main study group included 710 adult patients with cerebellar ectopia divided into subgroups according to the severity of cerebellar ectopia (less than 2 mm (CM0); 2-4 mm (CM0,5); 5 mm or more (CM1); 5 mm or more in combination with a pronounced prolapse of the brain stem below the foramen magnum (CM1,5)) as well as to the presence of «overcrowded¼ posterior cranial fossa (PF) and «small¼ PF. Clinical symptoms and bone phenotype of PF were analyzed. RESULTS: With an increase of the degree of cerebellar tonsils ectopia, an increase in the proportion of patients with «overcrowded¼ PF, syringomyelia, otoneurological and lower cranial nerve, brain stem, cerebellar disturbances was revealed. The phenomenon of «small¼ PF was observed in 81% of the main group. «Small¼ PF was associated with a greater proportion of patients with syringomyelia, and did not correlate with the level of ectopia and «overcrowded¼ PF. «Overcrowded¼ PF was found in 51% of patients and was associated with a greater frequency of combined pseudotumor and suboccipital CM1-caused headaches, as well as a greater degree of cerebellar ectopia. An analysis of the ratio of morphometric components of the PF phenotype in the studied population revealed a combination of three factors in 37% of patients; the proportion of isolated cerebellar ectopia did not exceed 10%. Among patients with clinical symptoms of CM1, the classic CM1 was detected only in 37% of patients. When comparing CM0,5 and CM1 groups, similar clinical and radiological characteristics were revealed, which may indicate a pathogenetic relationship between CM1 and tonsillar ectopia 2-4 mm classified by the authors as CM0,5. CONCLUSION: The study provided grounds for expanding the classification of CM1 in adults with the inclusion of CM0,5 form as well as for evaluation of the «small¼ and «overcrowded¼ PF phenomena in the diagnostic algorithm for patients with suspected Chiari malformation.

[Posterior reversible encephalopathy syndrome and arterial hypertension]. / Sindrom zadnei obratimoi entsefalopatii i arterial'naya gipertenziya.

OBJECTIVE: To identify a correlation between systolicdiastolic blood pressure (BP) and severity of clinical/radiological presentations in patients with posterior reversible encephalopathy syndrome (PRES). MATERIAL AND METHODS: Clinical and paraclinic data of patients with PRES hospitalized in the Republican Clinical Hospital, Kazan in 2010-2018 were analyzed. Nineteen patients were found, all of them were women, aged 18-67 years, mean age 33.50±15.03 years. Clinical and paraclinic data included anamnesis, neurological examination, neuroimaging, first measurements of systolic and diastolic BP after symptoms'onset. RESULTS AND CONCLUSION: Diastolic BP values can be associated with the incidence of depression of consciousness, systolic BP values - with the number of damaged structures. In total, BP is the significant factor implemented in the presence of endothelial dysfunction that defines the severity of encephalopathy.

[Significance of focal and nonfocal symptoms in the diagnostics of transient vertebrobasilar ischemic syndromes]. / Znachimost' fokal'nykh i nefokal'nykh simptomov v diagnostike tranzitornykh ishemicheskikh sindromov v vertebral'no-baziliarnoi sisteme.

AIM: Identification of clinical and paraclinic signs that are significant for the diagnosis of transient vertebrobasilar ischemia in patients with temporary brainstem, cerebellar or occipital dysfunction. MATERIAL AND METHODS: Clinical, anamnestic and instrumental data of 126 patients hospitalized in stroke unit with the diagnosis of vertebrobasilar acute cerebrovascular event, including patients with proposed stroke diagnosis at admission that was not confirmed later, were obtained and analyzed. RESULTS AND CONCLUSION: Significant clinical and paraclinic signs for differential diagnosis of transient vertebrobasilar ischemia and vertebrobasilar ischemia mimics were identified.

[Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA)]. / Rezul'taty randomizirovannogo dvoinogo slepogo mul'titsentrovogo platsebo-kontroliruemogo v parallel'nykh gruppakh issledovaniia éffektivnosti i bezopasnosti meksidola pri dlitel'noi posledovatel'noi terapii u patsientov v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta (ÉPIKA).

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS). MATERIAL AND METHODS: A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients' participation in trial ranged from 67 to 71 days. RESULTS: By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.

[The results of the multicenter pharmaco-epidemiological observational project on the use of mydocalm in the treatment of pain syndromes with the muscle spasm].

The prospective multicenter open noncomparative pharmaco-epidemiological observational project on the use of mydocalm in real clinical practice has been completed in 2013. The project has been performed in 2090 clinical/rehabilitation settings in 284 cities of 13 countries using the results of 35,383 patients. The project aimed to assess the safety of treatment (percentage of patients with adverse-effects) and pain relieving efficacy as well as patient's satisfaction with the treatment. In total, 6603 (19%) adverse-effects were recorded. Their severity was evaluated as mild in 84,48%, no serious adverse-effects were noted. The high efficacy of mydocalm in the treatment of pain syndromes with the muscle spasm has been demonstrated. The high level of tolerability and absence of the clinically significant increase of adverse effects in the combination with nonsteroidal anti-inflammatory drugs have been confirmed.

[Fever-induced refractory epileptic encephalopathy of children].

Fever-induced refractory epileptic encephalopathy of school-age children is a rare epileptic syndrome that causes difficulties in diagnosis at the initial stage of disease. It is characterized by sudden onset with multifocal refractory status epilepticus in previously healthy children with normal development. Later, children suffer from resistant focal epilepsy in the combination with cognitive deficit and behavioral difficulties. Authors describe a clinical case of fever-induced refractory epileptic encephalopathy of school-age children in a child of 7 years old. Aspects of etiology, pathogenesis, clinical manifestation, differential diagnosis, treatment and prognosis of the disease are discussed.

[Thymectomy and antibodies to acetylcholine receptors (AChR) in patients with myasthenia gravis in the early postoperative period].

Thymectomy and removal of the hyperplastic thymus have been performed in 21 patients with myasthenia. In 14 patients, thymectomy is performed through thoracoscopic access (TA), while in 7 cases through thoracotomic access (TT). The serum levels of antibodies to acetylcholine receptors (AChR) determined before and after surgery were increased in both groups of patients. Thus, thymectomy, regardless of the degree of clinical improvement in early post operative period, significantly increases the level of anti-AChR antibodies in the serum of patients in the early postoperative period compared to baseline. These changes may reflect the immune response to a stressful situation related to the traumatic surgery. It should be noted that the level of anti-AChR antibodies was significantly higher in a group of TT that may be related with a larger volume of the removed tissue.

[Efficiency of cerebrolysin in the diabetic polyneuropathy in patients with insulin-dependency diabetes mellitus].

78 patients with clinical features of diabetic polyneuropathy have been examined. 39 patients, who took cerebrolysin, compose the basic group, 39 patients, who made up control one, took milgamma. The dynamics of clinical signs of the diabetic polyneuropathy was evaluated by difference of points in the first and the second examination with the use of scales: NSC (Neuropathy Symptoms and Change) and NDS (Neuropathy Dysfunction Score); the visual analog scale (VAS) and changes of the signs of orthostatic test. For the detection of the effectiveness of treatment was estimated dynamics of neuropathic disorders represented in patient with diabetes mellitus types I and II (with secondary insulin-dependency), witch allowed to reveal the considerable therapeutic effectiveness of cerebrolysin in treatment of diabetic polyneuropathic disorders.

[Influence of cerebrolysin therapy on the dynamics of diabetic polyneuropathy symptoms].

60 patients with clinical features of symmetric diabetic polyneuropathy have been examined including 30 patients of main group who received cerebrolysin and 30 patients of control group treated with milgamma. The effectiveness of treatment was assessed by the dynamics of polyneuropathic disorders in scores on the Diabetic polyneuropathy scale and the NDS. Pain syndrome was measured with the VAS. The significant therapeutic effectiveness of cerebrolysin was revealed for some parameters measured.

The history of Kazan neurological school.

The historical prerequisites for the foundation and teaching of neurology at Kazan University are described; the relationship between the history of Kazan Imperial University Kazan medical university and neurology school is shown. Brief biographies of outstanding representatives of Kazan Neuroscience (D.P. Skalozubov, V.M. Bekhterev, L.O. Darkshevich, N.O. Kovalevsky, N.A. Mislavsky, A.V. Kibyakov, A.S. Dogel, A.V. Favorsky, L.I. Omorokov, and Y.Y. Popelyansky) are presented. The description of scientific interests of the Kazan neurological school and its specific features related to the one century period since 1885 are described.

The post-syrinx syndrome: stable central myelopathy and collapsed or absent syrinx.

Among 168 cases with neurologic findings of cervicothoracic syringomyelia and MRI findings of Chiari 1 malformation and/or underdevelopment of the posterior cranial fossa, 15 patients (9.1 %) had collapsed, flat syrinxes and 14 patients (8.3 %) did not have syrinxes. Both groups of patients had clinical findings of central myelopathy that had been stable for at least 3 years. Magnetic resonance imaging detected atrophy of the cervical spinal cord in both groups and spontaneous communications between the syrinx and the subarachnoid space in 3 patients of the group with collapsed syrinxes. Analysis of these results and review of the literature suggest that patients with clinical signs of syringomyelia and Chiari 1 malformation or underdeveloped posterior fossa, but with small or absent syringomyelitic cavities, have the "postsyrinx" state as a result of spontaneous collapse of distended syrinxes.

Clinical and neuroimaging features of "idiopathic" syringomyelia.

In some adult patients with cervical syringomyelia, MRI studies do not identify primary disease within the foramen magnum or spinal canal. To identify the etiology of this idiopathic type of syringomyelia, clinical features and posterior fossa (PF) measurements from 17 of these patients, 17 patients with Chiari I-type syringomyelia, and 32 control subjects were compared. Idiopathic syringomyelia and Chiari I-type syringomyelia manifested central cervical myelopathy and a small PF with narrow CSF spaces, suggesting that they develop by the same mechanism.

[Clinical and neuro-visual study of syringomyelia]. / Kliniko-neirovizualiziruiushchie issledovaniia pri siringomielii.

One hundred fifty one patients with syringomyelia of different duration were studied using magnetic resonance imaging (MRI). An association between syringomyilia cavitation and Arnold--Chiari malformation as well as cerebellar tonsils location was found. No definite relationship between syringomyelia course and degree of cerebellum ectopia was detected. With disease duration increasing, cross dimensions of spinal cord cavitation are getting smaller. This may be due to spontaneous cavitations collapse. The hypothesis is supported by flattened out cavitation phenomenon found by MRI on the axial spinal cord sections of 39 patients. Such deformation corresponds to spinal cord atrophy developing during long-term disease course.