LECTURES 
ORIGINAL INVESTIGATIONS
Perfusion computed tomography (PCT) is increasingly used to diagnose ischemic stroke (IS), as well as to identify candidates for thrombolytic therapy (TLT). The feasibility of using this technique in all patients within the therapeutic window has not yet been established.
Objective: to investigate cerebral blood flow according to PCT findings and its relationship to clinical and instrumental indicators and functional status of patients who had received TLT in the acute period of IS.
Patients and methods. 62 patients with acute IS who had received TLT were examined. All the patients underwent clinical, laboratory, and instrumental examinations and PCT, by assessing cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in 10 brain regions in accordance with the Alberta Score Program Early CT Score (ASPECTS). The total result of perfusion ASPECTS was calculated separately for CBV, CBF and MTT, as well as combinations of these parameters. The penumbra size was calculated as CBV minus MTT (CBV - MTT) ASPECTS, the infarct core size was measured as CBV + MTT ASPECTS.
Results. There was an increase in MTT in most regions of interest of the affected hemisphere as compared to the intact one and a predominance of reversible perfusion disorders. The averaged penumbra size constituted three zones according to ASPECTS. No relationship was found between ASPECTS scores and time after the onset of symptoms prior to hospital admission. Perfusion parameters, particularly penumbra size (CBV - MTT), were associated with the degree of stenosis in the contralateral common carotid artery, body mass index, and blood triglyceride level. Cerebral blood flow indices were also influenced by red blood cell counts and heart ejection fraction. The scores of the perfusion scales were correlated with those of the non-contrast scale. The data of the investigated ASPECTS variants correlated with the level of neurological deficit in patients, its course, and the functional outcome of acute IS.
Conclusion. The perfusion variants of ASPECTS have a high predictive value for patients' neurologic and functional status upon completion of the first treatment stage. The penumbra size (CBV - MTT ASPECTS) is a marker for the expected regression of neurological impairment during TLT. The infarct core size (CBV + MTT ASPECTS) determines the degree of neurologic deficit at a patient's discharge.
Objective: to study the clinical and psychopathological features of depressions with panic attacks.
Patients and methods. A total of 100 in- and outpatients aged 18 to 60 years, who had been treated in the S.S. Korsakov Clinic of Psychiatry for mild and moderate depression with panic attacks, were clinically examined using the psychometric scales: the Montgomery–Asberg Depression Rating Scale, the Atypical Depression Diagnostic Scale, and the Sheehan Clinical Anxiety Rating Scale.
Results. The clinical and psychopathological picture of depression with panic attacks differed significantly in three identified groups of patients with neurotic depression (ND), recurrent depressive disorder (RDD), and bipolar affective disorder (BAD). NDs with panic attacks were characterized by insignificant short-term symptoms of dreariness, indistinct anhedonia with the maximum manifestation of personality sensitivity, and a tendency to alcohol abuse. DDRs with panic attacks were inherent in melancholic and dreary symptoms, anhedonia, classical circadian mood fluctuations, and the most marked reactivity of mood. Depressions with panic attacks within BAD were typical of apathetic manifestations, hypersomnia, hyperphagia, and alcohol craving.
Conclusion. Depressions with panic attacks have psychopathological features depending on whether they develop within ND, RDR, or BAD.
Depressions in patients with schizophrenia in remission are quite common; however, their genesis and clinical features have been insufficiently studied.
Objective: to assess the clinical features of depressions occurring in patients with paroxysmal schizophrenia in remission.
Patients and methods. 88 patients with nonpsychotic depression who were diagnosed with paroxysmal schizophrenia in drug remission were examined. A total of 200 depressive episodes were analyzed. The patients' status was assessed according to the diagnostic criteria in the ICD-10 Classification of Depressive Disorders. For quantitative evaluation, the investigators used psychometric scales, such as the Calgary Depression Schizophrenia Scale and the PANSS Negative Subscale.
Results. There were two types of post-schizophrenic depressions: endogenous and reactive. Endogenous depressions are divided into postpsychotic depressions developing in remission and delayed depressive episodes; reactive depressions are divided into nosogenic and psychogenic.
Endogenous depressions represent a stage of the schizophrenic process; reactive ones are a schizophrenic patient's depressive reaction to a stressful situation. The latter occur in patients with a less severe schizophrenic defect, a higher critical attitude toward illness, and a better social and labor adaptation. Endogenous depressions have averagely a longer duration and a greater severity and besides anxiety symptoms, they include asthenic and apathetic symptoms; reactive depressions comprise only anxious and dreary manifestations.
Conclusion. Knowledge about the characteristics of depressions in schizophrenia will ensure their more accurate diagnosis and prescribe adequate therapy.
In the modern world, the discrepancy between biological and social rhythms in the presence of the existing genetic predisposition increases a risk for the occurrence and chronicity of depression. To solve this problem, various approaches, including a chronobiological one, are applied.
Objective: to explore the relationship between chronobiological characteristics and psychopharmacotherapy in patients with depression.
Patients and methods Eighty patients with depression, among whom women (68.7%) predominated, were examined. The age of the patients was 18–75 years (47.6±15.6 years). Their chronotype was identified using the Morningness–Eveningness Questionnaire (MEQ) to determine the type of circadian rhythm. Changes in the patients' status were clinically assessed utilizing the psychometric indicators.
Results. Sleep disorders were most pronounced in recurrent depression (4.1±1.1 scores) (Montgomery–Asberg Depression Rating Scale, MADRS, item 4). The inverted pattern of daily variations was more frequently observed in patients with a first depressive episode (p<0.05).
According to MEQ scores, the investigators identified three groups of patients with morning (5%), intermediate (65%), and evening (30%) chronotypes. At the same type, the latter chronotype was clearly associated with the positive family history of affective disorders, earlier onset of depression, a larger number of experienced episodes, a higher average duration of an episode in the history, younger age, and severe condition when visiting a physician's office required additional psychopharmacotherapy. It was more effective to use antidepressants in the morning, if the patient had an evening chronotype, and in the evening, if he/she had a morning/intermediate chronotype.
Conclusion. The patients with initially different chronotypes showed differences in the premorbid, onset, and course of the disease. The account of a chronotype can be considered as one of the approaches to optimize psychopharmacotherapy.
Objective: to investigate the efficacy and safety of Cavinton® Comforte (Vinpocetine) in patients with initial manifestations of chronic cerebrovascular disease (CVD) in outpatient neurological and therapeutic practice.
Patients and methods. The program included 4410 patients with a verified diagnosis of Stage I-II dyscirculatory encephalopathy. All the patients took Cavinton® Comforte 10 mg thrice daily for 3 months. The patients underwent neurological and general physical examinations, laboratory tests, functional diagnostic (electrocardiography, Doppler ultrasound), and neuroimaging techniques (magnetic resonance imaging).
Neuropsychological tests for attention, memory, visual-spatial and executive functions were used to assess cognitive impairment.
Results. Therapy with this drug showed a high efficiency in terms of both subjective characteristics and the data of neuropsychological tests for attention, memory, visual-spatial and executive functions. At the same time, the improvement was equally marked in young, middle-aged, and old patients. Positive changes in test results, as in patient complaints, were already evident after one month of treatment. A positive trend remained with the therapy continued for up to 3 months. More than 90% of physicians and patients assessed the efficacy and tolerability of treatment as good or excellent.
Conclusion. The investigation has demonstrated that it is appropriate to use the drug in patients at the early stages of chronic CVD. To further study the efficiency of this therapy in patients with chronic brain ischemia, it is advisable to conduct a comparative placebo-controlled investigation.
The clinical picture of Parkinson's disease (PD) includes a wide range of non-motor symptoms (NMS) that substantially worsen quality of life in patients. These symptoms are poorly diagnosed because they are not emphasized by patients themselves and their relatives. The low detectability of NMS can be attributable to the lack of awareness amongst specialists about a wide range of PD symptoms and to that of time at a visit for physician advice.
Objective: to evaluate the effectiveness of using the screening scale to timely detect NMS in PD.
Patients and methods. Examinations were made in 2 patient groups: 1) 95 PD patients aged 47 to 83 years (mean age, 64.91±7.66 years) (a study group); 2) 37 sex- and age-matched healthy individuals aged 48 to 77 years (mean age, 62.22±6.58 years) without signs of PD and PD of another etiology (a control group). To identify NMS, all the study participants filled out the NMSQuest scale.
Results. The mean number of NMS per patient with PD was 9.13±4.81 in the study group and 5.43±3.4 in the control group (p<0.001).
Symptoms, such as hypersalivation, hyposmia, dysphagia, nausea, vomiting, constipation, excessive sweating, decreased motivation, and a feeling of sadness, were statistically significantly more common in PD. There were no significant differences between the number of NMSs and the form of PD or convincing data on their relationship to age, disease stage, and the total equivalent dose of taken antiparkinsonian drugs (calculated with reference to levodopa).
Conclusion. The use of questionnaires in patients with PD allows the timely detection of the majority of NMSs. Given the limited time for counseling the patient, especially at an outpatient stage, the questionnaires should be filled out by the patient while he/she is waiting for a doctor's consultation.
Objective: to evaluate the efficiency of using computer stimulation programs (CSPs) for acute ischemic stroke (IS) in patients with cognitive impairment (CI).
Patients and methods. 81 patients aged 40 to 79 years with post-stroke CI (PSCI) were examined and randomized into two groups. A study group consisted of 45 people, including 31 and 14 patients with predementia CI and mild dementia, respectively; their median age was 61 [55; 68] years. A comparison group included 36 patients, including 21 and 15 patients with predementia CI and mild dementia; their median age was 64 [57; 70] years. In addition to standard stroke therapy, the study group received a ten-day correction cycle for CI, by using CSPs.
Cognitive functions (CF) were evaluated before and after classes, by applying a short mental status questionnaire (SMSQ), a battery of frontal lobe dysfunction tests (BFLDT), a clock drawing test, and a speech activity test.
Results. After 10 days of therapy (at 18–20 days of IS), the patients were observed to have statistically significant improvements of cognitive functions in all major neuropsychological scales: SMSQ, BFLDT, a clock drawing test, and a speech activity test (p>0.05).
Assessing the total indicators of SMSQ subtests in both groups showed that the study group achieved statistically significant differences in memory, time and place orientation, and concentration. In the study group, the total values of BFTLD subtests were also statistically better in indicators, such as speech fluency (by 33.0%), dynamic praxis (by 23.3%), a simple choice reaction (by 30.0%), and a complicated choice reaction (by 26.7%). At the same time, not only trained functions (attention, memory), but also other cognitive indicators improved. Re-examination demonstrated that the achieved results persisted 6-8 months later.
Conclusion. CSPs are a promising area of neurorehabilitation. The method is effective, easy-to-use; the patients can do lessons at hospital and at home after discharge in the presence of relatives or themselves. Further investigations will be able to evaluate the effectiveness of CSPs in patients with PSCI in the later periods of IS.
Sleep-disordered breathing (SDB) substantially impairs quality of life in a patient with amyotrophic lateral sclerosis (ALS) and promote the addition of serious respiratory and cardiovascular complications.
Objective: to identify the early signs of SDB in patients with various onset ALS using a comprehensive sleep assessment.
Patients and methods. A questionnaire survey using a comprehensive test for sleep disorders was conducted in 65 patients: 39 of them had ALS (male:female ratio, 25:14; age, 59 [51; 66] years) and 26 patients made up a control group (male:female ratio, 13:13; age, 54 [43; 59] years).
The questionnaire consists of 50 questions; the results were expressed as scores.
Screening portable polysomnographic study was conducted in patients with newly diagnosed ALS at the relatively early stages of the disease.
A total of 61 patients (32 women and 29 men; median (Me and the 25th and 75th percentile) age was 62 [55; 67] years) were examined. The disease duration was 12 [8.9, 27.1] months after the onset of the first symptoms. The body mass index was 25.7 [23.3, 28.7] kg/m2 . In the study
group, ALSFRSR [9] scores at study inclusion were 34.32 [32; 38]. Cervicothoracic onset ALS was present in 23 patients; 26 and 12 patients had bulbar and lumbosacral onsets, respectively.
Screening diagnosis of sleep was carried out using a Polymate YH-1000C portable polysomnograph (BMC, China) that registered nasopharyngeal flow (airflow through the nasal and oral cavities); thoracoabdominal movements (movements of the thoracic and abdominal walls); hemoglobin oxygen saturation of arterial blood ( SpO2); a snore sound through the microphone; and sleeping position (actography).
Results. The comprehensive screening study of breathing during sleep shows the underestimation of the complaints and symptoms of subclinical respiratory disorders in patients with ALS. Portable pulse oximetry at the early stages of the disease revealed changes in the nocturnal respiratory parameters that indicated a predisposition to the development of hypoventilation syndrome. Bulbar-onset ALS patients who had significantly higher apnea/hypopnea index (AHI) and oxygen desaturation (ODI) and lower mean SpO2 with the development of hypoventilation syndrome and, to a lesser extent, obstructive sleep apnea syndrome were most vulnerable to the development of SDB.
A correlation analysis revealed the impact of minimal SpO2, ODI, and apnea duration on cardiorespiratory parameters in ALS patients and the possibility of their use as markers to analyze of SDB and cardiac arrhythmias during screening studies in these patients.
Conclusion. The early detection and correction of respiratory failure symptoms can prolong patients' life and improve its quality. The screening study of nocturnal sleep and SDB in patients with ALS is a simple and informative method to evaluate a range of respiratory disorders, especially at the early stages of the disease.
Objective: to evaluate the safety, efficacy, and tolerability of the botulinum toxin A Relatox® in arm and hand spasticity after ischemic stroke in routine clinical practice.
Patients and methods. The instigation enrolled 7 patients after ischemic stroke (7 years ago) with the signs of upper limb spasticity. All the patients received combination treatment that involved daily kinesiotherapy sessions and electrical stimulation of the paralyzed limbs. Relatox® was once injected into the forearm muscles of the paralyzed arm 6 months or later after stroke. Muscles were chosen according to clinical and electromyographic findings. The patients' status was assessed before, 2 weeks and 3 months after injection.
There were changes in muscle tone, motor abilities of the hand, in the degree of self-service, the presence of subjective sensations, and the degree of local and systemic reactions. The efficiency of therapy was evaluated clinically (Ashworth scale, Frenchay test, Barthel index) and on the basis of an analysis of video monitoring a patient's status and of the consideration of care-givers' views.
Before included in the study, all the patients were treated with different types of botulinum neurotoxin type A made by other manufacturers.
Results. The clinical efficiency of local intramuscular injection of the botulinum toxin type Relatox® in combination with kinesiotherapy and electrical stimulation after 14 days and 3 months after injection was noted in all cases.
The good tolerability, efficacy, and long-term of action of relatox, which were comparable to those of other botulinum neurotoxin type A products, were noted during a 3-month follow-up. Neither side effects no adverse events were identified.
Conclusion. Accumulation of data on the doses and effects of drugs for the local therapy of post-stroke spasticity, which have been obtained by different clinical centers, and the possibility of choosing a medication will be able to improve treatment in such patients.
CLINICAL OBSERVATIONS
Neural tube defects are the most common central nervous system malformation. Dandy–Walker malformation (DWM) is a rare abnormality of the posterior cranial fossa, which is generally diagnosed in the prenatal period or early infancy.
The paper describes a case of the late clinical manifestation of DWM, which has caused syringomyelia. All variants of pathological changes within the Dandy–Walker complex very rarely become a cause of syringomyelia. Only four cases of DWM, in which syringomyelia was found in adults, are known.
The authors believe that formation of syringomyelia cysts in these patients is associated with the impaired circulation of normal cerebrospinal fluid between the superior cistern and the subarachnoid spaces of the spinal cord due to the caudal dislocation of the cyst formed in the fourth ventricle.
Decompression of the craniovertebral junction, by resecting the caudal portion of the cyst in the foramen magnum, and repair of the free communication between the superior cistern and the cerebrospinal fluid spaces of the spinal cord, which is complemented by duroplasty, are pointed out to be an optimal treatment in these patients.
REVIEWS
The paper considers the concept of vascular cognitive impairment (CI), no dementia, their epidemiology, risk markers and pathological basis.
It describes in detail the neuropsychological characteristics of CI, relevant diagnostic criteria, and clinical and neuroimaging diagnostic techniques. In addition to stroke, cerebral small vessel disease, which is characterized in the article in a modern light, is shown to play an important role in the development of moderate vascular CI. The course, prognosis of vascular cognitive impairment, and their determinants are discussed. Approaches to the treatment of the disease, including nicergoline therapy, and preventive measures with emphasis on physical activity are presented.
Complaints of dizziness and instability are the common reason for seeking a neurologist's advice at an outpatient visit and can be the frequent reason for emergency hospitalization.
Difficulty in diagnosing the causes of dizziness and instability is due to a diversity of diseases manifested by these symptoms. The list of etiological factors includes peripheral and central vestibular lesions and unrelated nervous system diseases. In a number of cases, dizziness and instability are concurrent with cognitive impairment. Complaints of poor concentration and memory, dizziness and instability can often be associated with brain degenerative and/or vascular lesions, as well as with pathological mood changes and anxiety disorder.
The diagnosis of these diseases requires neurovestibular examination, cognitive testing, and assessment of the emotional status of patients. Early detection of the causes of dizziness and memory disorders ensures better treatment results. There are different approaches to therapy for dizziness and cognitive impairment: drug and non-drug correction techniques (vestibular rehabilitation and cognitive training). Biofeedback procedures were shown to be highly effective.
The effect of tanakan in treating patients with involvement of the peripheral vestibular system and brain structures is discussed
Many antiepileptic drugs (AEDs) have a short half-life (T1/2) with a wide fluctuation from peak to trough blood concentrations. According to this pharmacokinetic profile, there may be both adverse events (AEs) due to the increase in a blood drug concentrations and seizures as a result of its fall, which ultimately lowers patient adherence to therapy.
Pharmaceutical technologies ensuring a delayed release of the active ingredient can make the concentration of a drug more stable and therefore reduce the frequency and severity of AEs, enhance the efficiency of therapy, compliance, and retention of the patient on AEDs. The emergence of a new sustained-release levetiracetam formulation in neurologists' practice greatly enhances the possibilities of epilepsy therapy.
Chronic cerebral circulatory disorders (CCCDs) are a group of syndromes manifested by cognitive, emotional disturbances and less commonly motor and sensory neurological symptoms, which is heterogeneous in the mechanisms of development. The prevention of CCCDs involves the control of blood pressure and glycemia and the use of antiplatelet and other drugs; however, the efficiency of these measures for an already formed defect is low.
The paper emphasizes the need for careful consideration of a patient's status at the beginning of treatment measures. Combined treatment, including secondary prevention of cerebrovascular disease, drugs that improve cerebral blood circulation and metabolism, and non-drug techniques, can be expected to have a more significant clinical effect. The possibilities of drug therapy, including the use of vinpotropile, in patients with CCCD, are considered.
EXPERIMENTAL STUDIES
Organic lithium salts are a promising area for searching for effective and safe neuroprotective drugs. By using chronic bilateral common carotid artery occlusion models, the authors have previously found that lithium gluconate and lithium citrate are effective agents to prevent a neurological deficit in brain ischemic or neurodegenerative damages. The use of organic lithium salts in brain ischemia leads to their targeted accumulation in the frontal lobes of the brain and in the cerebrospinal fluid, normalizing trace elemental homeostasis in the brain Objective: to compare the neuroprotective effects of different lithium salts (chloride, carbonate, ascorbate, and citrate).
Material and methods. A neurocytological study was performed using a glutamate-induced stress model in cultured granular neurons (CGNs).
The state of CGNs was monitored daily and at each experimental stage, by viewing in an inverted phase contrast microscope. The final concentrations of the test substances in the culture medium were 0.1, 0.2, and 0.5, and 1 mM. The survival of CGNs was quantified by directly counting the neurons with intact morphology in 5 fields of vision. Five experiments were carried out for each substance. The number of neurons with intact morphology in the control cultures was taken as 100% survival.
Results. Lithium chloride and lithium carbonate in the studied range of concentrations did not show significant neuroprotective properties.
Lithium ascorbate and lithium citrate, on the contrary, significantly increased the survival of neurons in mild, moderate and severe glutamateinduced stress. Lithium citrate at a concentration of 0.2 mM increased the survival rate of CGNs by an average of 30% (p < 0.003). The active neuroprotective principles of lithium citrate were shown to be both lithium ion and citrate anion. These positive qualities of the test organic lithium salts are explained primarily by the fact that ascorbate and citrate anions contribute to the enhanced transport of lithium ions into the cells through appropriate ion channels for the transport of organic acids (SLC13A5, etc.).
Conclusion. Lithium ascorbate and lithium citrate were confirmed to have an immediate neuroprotective effect on cerebellar CGNs. Treatment of CGNs with lithium citrate showed a 30% increase in cell survival during glutamate-induced stress.
ISSN 2310-1342 (Online)
