The Role of a Pathological Interaction between ß-amyloid and Mitochondria in the Occurrence and Development of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in existence. It is characterized by an impaired cognitive function that is due to a progressive loss of neurons in the brain. Extracellular ß-amyloid (Aß) plaques are the main pathological features of the disease. In addition to abnormal protein aggregation, increased mitochondrial fragmentation, altered expression of the genes involved in mitochondrial biogenesis, disruptions in the ER-mitochondria interaction, and mitophagy are observed. Reactive oxygen species are known to affect Aß expression and aggregation. In turn, oligomeric and aggregated Aß cause mitochondrial disorders. In this review, we summarize available knowledge about the pathological effects of Aß on mitochondria and the potential molecular targets associated with proteinopathy and mitochondrial dysfunction for the pharmacological treatment of Alzheimer's disease.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied; mean age was 54.6 ± 4.5 years; duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10-14. The third visit was on day 30 of out-patient treatment. Assessment of patients' status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression; less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

[Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX]. / Opredelenie rasprostranennosti postkovidnogo sindroma i otsenka effektivnosti preparata Korteksin v terapii nevrologicheskikh narushenii u patsientov s postkovidnym sindromom. Rezul'taty mnogotsentrovoi nablyudatel'noi programmy KORTEKS.

OBJECTIVE: To study the prevalence of clinical manifestations of postcoid syndrome in patients at an outpatient neurological appointment, to evaluate the effectiveness of therapy regimens using Cortexin at doses of 10 mg and 20 mg IM for 10 days. MATERIALS AND METHODS: 674 neurologists from all regions of the Russian Federation, Azerbaijan, Kyrgyzstan and Kazakhstan took part in the study. A total of 979 COVID-19 patients were recruited. The average age is 54.6±0.45 years. The duration of the transferred SARS-CoV-2 days and from 1 month or more 12. 3 visits were carried out: 1 on the day of treatment (assessment of complaints, analysis of scale indicators, prescription of the drug Cortexin in doses of 10-20 mg/m for 10 days). 2 (telephone survey) visit for 10-14 days, 3 visit - for 30 days at the reception. The condition was assessed using the Asthenia Assessment Scale (MFI-20), the Brief Mental Status Assessment Scale (MMSE questionnaire), the Schulte test, and the Subjective Treatment Quality Assessment Scale. RESULTS: The daily proportion of patients with complaints after a previous coronavirus infection was 30% in the total structure of neurological admission. The most common complaints: fatigue, general weakness, decreased memory and concentration, dizziness, sleep disturbance, irritability, aggression, shortness of breath, pain syndromes, excessive sweating, anosmia, hyposmia, perverted taste of paresthesia, hair loss, blurred vision, unstable blood pressure, tachycardia, allergic reactions, menstrual irregularities, erectile dysfunction, apathy, panic attacks, suicidal thoughts, depression, refusal to eat meat. CONCLUSION: There was no significant correlation of clinical symptoms with the severity of COVID-19, the percentage of lung tissue damage, and different periods of postcovid syndrome. The clinical efficacy of the drug Cortexin in dosages of 10 and 20 mg for the correction of cognitive and asthenic disorders has been proven. Revealed anti-anxiety, antidepressant and anxiolytic activity of Cortexin is more pronounced when using a dosage of 20 mg.

[The evaluation of hyperkineses in hepatocerebral dystrophy (Wilson-Konovalov disease) from the position of the theory of muscle spindles].

OBJECTIVE: To obtain evidence for the possibility of considering hyperkineses in hepatocerebtal dystrophy from the position of the theory of muscle spindles. MATERIAL AND METHODS: We examined 27 patients: rigid-arrhythmic-hyperkinetic form was diagnosed in 2 patients, trembling-rigid in 8, trembling in 16 and extrapyramidal-cortical in 1. Electromyography of different muscles in resting state and functional loadings taking into account surgical intervention was the main method of the study. RESULTS AND CONCLUSION: An analysis of electrophysiological results based on hyperkinesis variant (torsion dystonic, choreoathetoid etc) revealed a role of the striatal pallidal system in the anomalous control of static and dynamic γ-motorneurons and involvement of spinal reflexes in forced movements. This hypothesis may help to deeply understand the genesis of extrapyramidal dyskinesia and more reasonably select a stereotaxic target in surgical treatment.

[The evaluation of tremor in Parkinson's disease from the view of the muscular spindle theory].

The author suggests a hypothesis on the origin of tremor. The hypothesis is based on the results of electromyographic (EMG) study using cutaneous electrodes in patients with tremor-rigid form of Parkinson's disease before and after the stereotaxic surgery. The natural afferent impulses from receptive areas of the organism, in particular, from proprioreceptors or muscle filaments, are thought to be the energetic basis of hyperkineses. The wakeful brain conducts the excessive non-specific information along the inhibitory premotor-caudata-pallidal-thalamic-motor pathway (caudatal loop). This mechanism does not work in patients with Parkinson's disease due to the deficit of brain dopamine that affects the control over static gamma-motoneurons. On the spinal level, a myotatic unit with the involvement of the static γ-motoneuron, nuclear chain intrafusal fiber, pathway 1a, phasic γ-motoneuron and phasic oxidative extrafusal muscle fiber is responsible for the development of trembling hyperkinesis. The hypothesis allows to understand deeper the pathogenesis of tremor and to evaluate the results of surgical treatment as well.

[Neurophysiological and neurohistological analysis of striatal hyperkineses in the treatment with stereotaxic method].

A stereotaxic method has been used for the electrostimulation with the following electrolytic destruction of brain structures in 86 patients (54 male and 32 female, aged from 6 to 52 years). The sample included 16 patients with torsion dystonia, 36 - with athetosis, 25 - with choreoathetosis and 9 with Huntington's chorea. The decrease of intensity of hyperkineses has been achieved in 81% of patients, no effect has been found in 19%, 1 patient died. Striatum, thalamus, motor and premotor neocortex, Cajal nucleus, dentate nucleus of cerebellum, subthalamic area (fields H7 and H2 of Forel) were used as stereotaxic targets. Data on the neurophysiological basis of changes of the pathological impulsion underlying hyperkineses are obtained. This finding has been confirmed by some neurohistological signs.

[Neurophysiologic and neuropathological analysis of Parkinson's disease and its treatment with stereotaxic method]. / Neirofiziologicheskii i neiromorfologicheskii analiz bolezni Parkinsona i ee lechenie stereotaksicheskim metodom.

Complete stopping of tremor or its essential reduction have been achieved in 55 of 66 patients with Parkinson's disease. In 3 cases, there was a fatal outcome. The microstructural changes of nigrostriatal, thalamus and neocortex neurons are presented, and biopotentials led from these structures, along with clinical and neurophysiological effects of electrostimulation of thalamic and subthalamic regions, are evaluated. The results obtained in the study are used for explanation of tremor mechanism.

[The application of variational cardiointervalography for optimization of anesthesia in outpatient surgery]. / Primenenie variatsionnoi kardiointervalografii dlia optimizatsii anesteziologicheskogo posobiia v khirurgii odnogo dnia.

The vegetative regulation condition was investigated by the method of variation cardio-interval-graphy in patients who underwent the intravenous anesthesia in the outpatient setting. The experience of using, on the differential basis, the sympathomimetic and vagotonic anesthetics for different-type vegetative tonus was analyzed. An optimal state in the vegetative regulation of the cardiovascular system, a stable hemodynamics and an adequate post-narcosis rehabilitation in the anesthetic management of one-day surgery were ensured owing to the suggested method in choosing an anesthetic.

Electrical stimulation of the brain in Wilson-Konovalov hepatocerebral dystrophy (a neuromorphological and neurophysiological analysis).

Stereotaxic surgery was performed in 27 patients. Complete elimination of or significant reductions in hyperkinesia were obtained in 17 cases; five patients died. There was no correlation between the severity of clinical manifestations of hepatocellular dystrophy and the relatively normal quantitative measures of cortical and subcortical biopotentials, which were produced on a background of microstructural changes affecting neurons in these regions. It is suggested that qualitative significance of these biopotentials is that they carry an excess pathological spike activity resulting in hyperkinesia. This is supported by the fact that hyperkinesia was suppressed after surgical destruction of the ventrolateral nucleus of the thalamus and subthalamic structures.

Functional state of segmental motoneurons in Wilson-Konovalov hepatocerebral dystrophy.

Stimulatory electromyography was used to investigate 12 patients, and chronaximetric investigations were performed in 18. Peak H-potential amplitudes indicated reductions in reflex excitability in the motoneuron pool. The stimulus size required for inducing threshold H-reflexes demonstrated a high level of reflex excitability among those alpha-motoneurons probably involved in generating hyperkinesia. Motor response parameters showed the direct electrical excitability of motor units to be elevated. Changes in H-reflex and M-response parameters demonstrated functional rearrangement of the movement analyzer after stereotaxic surgery. The functional states of the alpha- and gamma-systems are discussed.

[Neurologic manifestations of sarcoidosis]. / Nevrologicheskie proiavleniia sarkoidoza.

126 patients with histologically verified mediastinal-pulmonary legions were examined in terms of neurologic manifestations of sarcoidosis. Systemic psychoneurologic observation of all patients was performed by continuous method. Neurologic disorders were nonmalignant, chronic, latent or transitory. Stable, acute or severe manifestations were registered quite seldom. Sensory, autonomic, neuroendocrine and neuropsychologic disorders prevailed in clinical picture.

[The immune response to brain contusion with hematoma-induced compression]. / Immunnyi otvet na ushib mozga s sdavleniem gematomoi.

Non-specific immune responses, cell-mediated immunity, and humoral immunity were analyzed in 35 patients with acute subdural hematomas vs. 55 healthy controls. The importance of prophylactic immunomodulation in prevention of infections and other clinically significant long-term complications after head trauma was demonstrated.

[The function of the segmental motoneurons in Wilson-Konovalov's hepatocerebral dystrophy]. / Funktsional'noe sostoianie segmentarnykh motoneironov pri gepatotserebral'noi distrofii Vil'sona--Konovalova.

12 patients were examined by means of stimulative electromyography. Chronaximetric studies were carried out in 18 patients. The maximal amplitude of H-potential revealed the decrease of reflex excitability of the motoneurons pool. The stimulus value which is necessary for evoking H-reflex of liminal size testified the high reflex excitability of some alpha-motoneurons part. These motoneurons may take part in hyperkinesis development. The direct electrical excitability of motor units was elevated that was confirmed by motor response values. The motor analyzer functional rearrangement was revealed after stereotaxic operations as evidenced by dynamics of H-reflex and M-response parameters.

[The electrical excitability of the peripheral motor neuron in parkinsonism]. / Elektricheskaia vozbudimost' perifericheskogo dvigatel'nogo neirona pri parkinsonizme.

Chronaximetry and stimulation electromyography were used in examination of 22 and 18 parkinsonian patients, respectively. The maximal amplitude of H-potential, the ration of the amplitude of the reflex to motor response and other parameters evidenced reduced reflex excitability of the motor neurone pool. The intensity of the stimulus sufficient to evoke threshold H-reflex indicated enhanced reflex excitability of the motoneurons which are likely to form passive tremor. As shown by motor response parameters, direct electric excitability of the motor units was high. Following stereotactic treatment, H-reflex and M-response shifted in the direction of increasing motor units excitability. These changes characterize functional rearrangement of the motor analyzer and correspond to a clinical response.

[Tremulous hyperkinesia in the parkinsonism syndrome and its electromyographic characteristics]. / Drozhatel'nyi giperkinez v sindrome parkinsonizma i ego élektromiograficheskaia kharakteristika.

Basing on the results of global electromyography performed for 51 patients with parkinsonism, it is concluded that volley muscular activity may be related with neurophysiological segmentary reflexes: discharge of alpha-motoneurons from primary endings of the muscle spindle; autogenic, reciprocal and feedback inhibition of alpha-motoneurons.

[Nonspecific resistance and the immunological indices in brain contusion]. / Nespetsificheskaia rezistentnost' i nekotorye immunologicheskie pokazateli pri ushibe golovnogo mozga.

As many as 55 healthy persons and 69 victims with brain contusion of medium and severe degree were examined. Inhibition of cellular immunologic reactions and attenuation of nonspecific resistance as well as increase of immunoglobulins, immune complexes and cerebral antibodies were revealed. These changes were found to be more pronounced in a severe brain contusion.

[The electromyographic analysis of trembling hyperkinesis in Wilson-Konovalov's hepatocerebral dystrophy]. / Elektromiograficheskii analiz drozhatel'nogo giperkineza pri gepatotserebal'noi distrofii Vil'sona--Konovalova.

Global electromyography was applied in the examination of 20 patients with Wilson-Konovalov's hepatocerebral dystrophy before and after stereotaxic operations. The origin of volley muscular activity is explained on the basis of segmental reflexes known in neurophysiology: indirect relief of alpha-motoneurons from the primary terminals of the spindle, autogenous, recurrent and reciprocal inhibition of alpha-motoneurons.