LECTURES
diagnosis of ICH and its clinical neuroimaging diagnostic algorithm are presented.
To implement the treatment strategy, it is necessary to adhere to a multidisciplinary personalized approach to pain management with active patient participation. Cognitive behavioral therapy (CBT) occupies an important place in the treatment of CPP. There is clinical and neurophysiological evidence of the efficiency of CBT in patients with CPP, a protocol has been developed for the combined use of CBT and physical therapy. CBT is recommended to be included in a comprehensive treatment and rehabilitation program for patients with CPP.
ORIGINAL INVESTIGATIONS
Phenazepam is a benzodiazepine tranquilizer that is widely used in Russia. The drug is metabolized by cytochrome P450 3A (CYP3A) isozymes. Since their substrates have an affinity for P-glycoprotein, the polymorphic variants in the ABCB1 gene may affect the safety of this drug.
Objective: to analyze associations between the CYP3A5, CYP2C9, CYP2C19, CYP2D6 and ABCB1 gene polymorphisms and the safety of phenazepam treatment for alcohol withdrawal syndrome (AWS).
Patients and methods. The investigation enrolled 102 patients diagnosed with uncomplicated AWS (IDC-10 code F10.30). All the patients were followed up for 6 days within which they took phenazepam. 5-ml venous blood samples were collected from each patient for genotyping. The carriage of CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*17, CYP2C9*2, ABCB1 3435C>T, 1236C>T, and 2677G>T/A polymorphic variants was determined by a real-time polymerase chain reaction assay. Therapy safety was evaluated using the UKU Side-Effect Rating Scale on day 6. Statistical analysis was carried out with SPSS Statistics 21.0. Haplotype and combinatorial analyses were performed using SNPStats.
Results and discussion. The greater subjective severity of adverse reactions (ARs) was shown for the homozygotes of ABCB1 1236C>T CC (odds ratio (OR), 2.154; 95% confidence interval (CI), 1.271–3.650; p=0.014) and ABCB1 2677G>T GG (OR, 2.154; 95% CI, 1.271–3.650; p=0.014). On the contrary, a combinatorial analysis revealed the role of ABCB1 3435C>T, 1236C>T, and 2677G>T polymorphic alleles as predictors for the greater subjective severity of ARs. The following statistically significant polymorphic variant combinations were ABCB1 3435-1236–2677 and T-T-T-CYP3A5*3 isozymes (OR=5.03; 95% CI, 1.65–15.34; p=0.0056); T-T-T-CYP2C9*1 (OR=3.61; 95% CI, 1.31–9.92; p=0.015); T-T-T-CYP2C19*1 (OR=2.52; 95% CI, 1.05–6.08; p=0.042). Attention disorders were also established to be associated with the carriage of T-T-T-CYP2D6*1 (OR=2.58; 95 CI, 1.08–6.13; p=0.035).
Conclusion. The carriage of ABCB1 3435-2677-1236 (T-T-T) haplotype is significantly associated with the greater severity of ARs in phenazepam-treated patients with AWS.
An assessment of not only the degree of stenosis, but also the structure of atherosclerotic plaques (ASPs) in the carotid arteries can reveal atheromas that are dangerous for the development of cerebrovascular events in asymptomatic individuals.
Objective: to study the echostructure of ASPs in patients in the acutest period of carotid ischemic stroke (IS) and to analyze predictors for its development according to ultrasonic duplex scanning (DS).
Patients and methods. A study group included the results of DS in 668 patients (370 men and 298 women aged 63±11 and 69±9 years, respectively) with IS in the middle cerebral artery bed. Out of 222 patients, 160 (72.1%), 56 (25.2%), 4 (1.8%), and 2 (0.9%) people had atherothrombotic, cardioembolic, hemodynamic, and lacunar subtypes of IS, respectively. A control group consisted of 903 asymptomatic individuals matched to the patients for gender and age.
Results and discussion. In patients with IS, carotid stenoses were characterized by the higher degree of a reduction in the lumen of both the internal carotid arteries (ICA): on the right (r) (53±23%) and left (l) (54±24%) sides, and the common carotid arteries (CCA): on both sides (40±12%) compared to asymptomatic individuals: rICA (40±14%), lICA (39±15%); and both CCAs (32±9%). At the same time, ASPs in the carotid arteries in the acutest period of IS were significantly more frequently homogeneous hypoechoic (21.2%) or heterogeneous with a hypoechoic component (25.6%), and also more frequently had an uneven contour in the rICA (41.3%) and lICA (33.6%), compared to those in asymptomatic individuals (hypoechoicity (7.0 and 5.6%, respectively); the uneven contour was in the rICA (3.2%) and lICA (4.0%). The study indicated that a set of echo signs (the degree of stenosis in the ICA and CCA; the homogeneity and hypoechoicity of ASP in the ICA; the uneven contour of ASP in the carotid arteries) was formed for primary ultrasound carotid stenosis screening carried out using a routine DS
technique. Additional studies that can more accurately identify ASPs that are dangerous for the development of cerebral vascular events are recommended for asymptomatic individuals with ASP and the above signs, which will determine their treatment policy.
Conclusion. Atheromas in the carotid arteries in the acutest period of IS are different from those in asymptomatic individuals by a number of features identified during routine ultrasonic DS. The most valuable individual prognostic sign of the development of carotid IS was the uneven contour of ASP in the carotid arteries.
Quality of life indicators are widely used to determine the efficiency of various medical therapies for cervical myelopathy; however, but these have been insufficiently studied in assessing the results of surgical treatment for this pathology. In addition, the results of surgical treatment for cervical myelopathy are observed to be unsatisfactory in 15–20% of cases, which indicates the need to develop new techniques and to improve existing ones for its correction. Direct electrical stimulation of the spinal cord may become one of the promising areas.
Objective: to comparatively analyze the efficiency of various surgical treatments for cervical myelopathy, by assessing the quality of life indicators in the patients.
Patients and methods. The investigation enrolled 92 patients with cervical myelopathy: 29 (49.2%) patients underwent posterior spinal cord decompression via laminectomy; in 17 of them, that was supplemented with the electrodes placed on the posterior columns of the spinal cord for its postoperative direct electrical stimulation; 63 (50.8%) patients underwent anterior spinal cord decompression, 12 of them had electrodes placed on the anterior horns of the spinal cord.
Results and discussion. After posterior spinal cord decompression with laminectomy, there were increases in physical functioning from 36.7±2.1 to 49.6±3.1 arbitrary units (arb. unit) (p<0.05) and in role physical functioning from 39.4±2.6 to 51.3±2.6 arb. unit (p<0.05) and a decrease in pain sensations from 51.6±2.6 to 30.2±0.8 arb. unit (p<0.05). Electric stimulation of the spinal cord caused increases in physical functioning from 40.3±3.6 to 61.3±2.8 arb. unit (p<0.05) and in role physical functioning from 36.7±1.6 to 69.4±1.6 arb. unit (p<0.05) and a reduction in pain sensations from 49.8±2.4 to 21.0±1.2 arb. unit (p<0.05). The similar trend as also observed in anterior spinal cord decompression concurrent with corporodesis at the cervical level after direct electrical stimulation of the spinal cord. Physical functioning increased from 42.0±3.1 to 57.6±1.4 arb. unit (by 26.4%; p<0.05) and mental health improved (only by 14.3%). After isolated anterior spinal cord decompression with corporodesis, physical functioning was 48.4±0.9 arb. unit by the end of the third month follow-up (p<0.05); following that in combination with electrical stimulation, physical functioning was 57.6±1.4 arb. unit (p<0.05). The posttreatment levels of viability, social functioning, role emotional functioning, and mental health were significantly lower in patients with a disease duration of more than 6 years than in those with that of less than 3 years.
Conclusion. Posterior and anterior spinal cord decompression with laminectomy for cervical myelopathy increases the indicators of physical functioning and role physical functioning and reduces pain sensations. The additional use of electrical stimulation of the spinal cord allows one to increase role physical functioning.
Neck pain is a widespread disease that significantly impairs quality of life in patients. General approaches to managing patients with acute neck pain are generally consistent with the recommendations for the treatment of acute back pain: its pharmacotherapy includes nonsteroidal antiinflammatory drugs (NSAIDs) and muscle relaxants.
Objective of the observational program: to compare the efficiency of treatment for nonspecific acute neck pain with tolperisone 150 mg/day, followed by dose escalation up to 450 mg/day, versus meloxicam 15 mg/day for 14 days.
Patients and methods. The observational program covered 37 patients aged 18–65 years who were diagnosed with acute nonspecific neck pain; of them 19 patients made up Group 1 and 18 formed Group 2. Group 1 was prescribed tolperisone (Calmirex) as tablets: 150 mg/day on day 1, 300 mg/day on day 2, and 450 mg/day on day 3 until the end of therapy. On day 1 of the investigation, Group 2 received meloxicam 15 mg/day in two divided doses (7.5 mg in the morning and evening). At baseline and on days 7 and 14 days of therapy, the investigators assessed the dynamics of pain using a visual analogue scale (VAS), as well as its intensity at rest and during movement; neck disability index (NDI) and recorded adverse events.
Results and discussion. The two groups showed a significant decrease in pain intensity on both 7 and 14 days of therapy. The rate of effect onset was significantly faster in the meloxicam group. On day 14 of treatment, both patient groups showed a considerably better functional state in terms of activity limitations due to neck pain (NDI); patients' perceptions of therapy were rated as good and excellent in most cases. On 14 days of therapy, the degree of pain reduction in the meloxicam group was higher, but the differences with that in the tolperisone group did not reach statistical significance, which can indicate the comparable efficacy of the drugs.
Conclusion. The data of this observational program are consistent with the recommendations for the treatment of nonspecific acute neck pain, which indicate NSAIDs and muscle relaxants as drugs for the treatment of this disease.
Objective: to comparatively study several nonsteroidal anti-inflammatory drugs (NSAIDs) (their analgesic effect; dynamics of quality of life; side effects, such as NSAID-gastropathy and gastric dyspepsia) in acute pain in the neck and back (dorsalgia).
Patients and methods. The investigators followed up 120 patients (4 groups, each having 30 people) with acute dorsalgia who took different oral NSAIDs for 7 days: long-acting ketoprofen, aceclofenac, naproxen, and dexketoprofen (Flamadex). To evaluate their possible side effects, dyspepsia symptoms were monitored and blood pressure (BP) was measured daily; gastroscopy was repeated after completion of a treatment cycle. The Nottingham Quality of Life Questionnaire and the Visual Analogue Scale (VAS) for pain were used.
Results and discussion. A gradual and substantial reduction in pain measured according to VAS was noted in all the NSAID-treated groups. The intensity of pain syndrome decreased faster in the dexketoprofen group; the analgesic effect of naproxen and long-acting aceclofenac was significantly less (p=0.012 and 0.002, respectively). This patient group showed a tendency to maximum improvement according to the Nottingham Quality of Life Questionnaire and VAS. Elevated BP was observed in all the groups, but statistically significantly more frequently in the naproxen group (p=0.05). Gastric dyspepsia was also registered in all the groups, but a tendency to its lower frequency was seen in the
dexketoprofen group.
Conclusion. Dexketoprofen showed fewer side effects and a more pronounced analgesic effect than ketoprofen, aceclofenac, and naproxen in acute dorsalgia.
Selective serotonin reuptake inhibitors (SSRI)-induced apathy syndrome occurs in 5–20% of patients taking these drugs.
Objective: to investigate the possibility and advantages of switching patients with SSRI-induced apathy to treatment with a SSRI and norepinephrine reuptake inhibitor.
Patients and methods. The investigation enrolled 105 depressive patients without psychotic symptoms, who were observed to develop symptoms of SSRI-induced apathy during SSRI antidepressant monotherapy for at least 6 months. The patients were randomized to groups: 1) 35 patients were switched to milnacipran (Ixel 50–100 mg/day) with simultaneous antidepressant replacement; 2) 35 patients were prescribed milnacipran with a 2-week gradual discontinuation of the previous SSRI; 3) 35 patients were switched to combined therapy with milnacipran 50–100 mg/day and sulpiride (Eglonyl 50 mg/day). The latter was prescribed to test the hypothesis for the benefits of combined correction of SSRI-induced apathy syndrome. The duration of the investigation was 3 months. Changes in the condition of the patients were assessed during their visits before and 1, 2, 4, 8, and 12 weeks after changing therapy. The efficiency of antidepressant therapy was studied using the 21-item Hamilton Depression Rating Scale (HDRS-21) and the Clinical Global Impression (CGI) rating scale; the changes in the severity of asthenic manifestations were examined according to a subjective asthenia assessment (Multidimensional Fatigue Inventory (MFI-20)). The UKU side effect rating scale was used to verify side effects.
Results and discussion. A significant (p<0.05) pronounced thymoleptic effect of various treatment regimens (simultaneous and gradual replacement with monnacipran monotherapy, as well as a milnacipran-sulpiride combination) was confirmed at week 4 of treatment. There was a reduction in SSRI-induced apathy syndrome when switching to treatment with milnacipran or milnacipran-sulpiride in 71.4–80% of patients. Different therapy replacement regimens showed varying changes in the reduction of heterogeneous asthenoapathic symptoms. A favorable safety profile was established for both monotherapy with milnacipran and its combination with sulpiride.
Conclusion. The antidepressant milnacipran (up to 100 mg/day) exhibits a high efficacy and a good tolerance in case of SSRI-induced apathy syndrome, as well as by a pronounced thymoleptic effect, including when combined with the antipsychotic sulpiride (50 mg/day).
Objective: to elucidate the frequency and pathogenesis of myofascial pain syndrome (MFPS) in chronic nonspecific lower back pain (CNLBP) and to optimize the diagnosis and treatment of MFPS in CNLBP.
Patients and methods. The investigation covered 121 patients with CNLBP. The patients' mean age was 42.1±10.5 years; the pain duration was 7.9±4.3 months. The possible causes of CNLBP were determined: these were facet joints (FJs); sacroiliac joints (SIJs); skeletal muscles with the development of MFPS; MFPS concurrent with FJs; MFPS concurrent with SIJs. Twenty patients had MFPS only (its mean duration was 5.3±2.2 months; the mean pain intensity scores were 6.5±1.1 on a numerical rating scale). Six patients underwent examinations of open biopsy specimens of the muscle straightening the spinal column; a comparison group consisted of 3 healthy women matched for age and gender. The patients were prescribed therapy with aceclofenac 200 mg/day in combination with tolperisone 450 mg/day and nondrug therapy (cognitive behavioral therapy and kinesio- and ergotherapy). When the treatment was insufficiently effective, ultrasonography of the muscle straightening the spinal column was additionally performed; a local anesthetic was injected into myofascial trigger points (MTPs).
Results and discussion. MFPS was a cause of pain syndrome in 63 (52%) patients, while MFPS this was an isolated cause of pain in 20 (16.5%) cases and was concurrent with FJ osteoarthritis in 23 (19%), and with SIJ dysfunction in 20 (16.5%). Muscle ultrasonography in patients with MFPS revealed MTPs, whereas examinations of biopsy specimens of the muscle straightening the spinal column showed no evidence of necrosis, fibrosis, or inflammatory infiltration in the presence of transformation of the myosin phenotype, by increasing the proportion of rapidly fatigued type II muscle fibers. The results of sodium dodecyl sulfate (SDS) gel electrophoresis indicated a decrease in the content of titin and nebulin, the sarcomeric cytoskeletal proteins involved in maintaining muscle contractility. A two-week cycle of therapy with aceclofenac and tolperisone reversed pain syndrome in 5 (25%) of the 20 patients and reduced the intensity of back pain in 15 (75%), but the pain increased during physical exercise and impeded active rehabilitation. The additional administration of anesthetics into MTPs and the continuous intake of aceclofenac and tolperisone in combination with kinesiotherapy could relieve pain syndrome and enhance motor activity.
Conclusion. More than half of the patients with CNLBP had MFPS only or concurrent with joint pathology (FS and FJs). The changes found in the back muscle biopsy specimens of patients with CNLBP are potentially reversible and can be reversed during kinesiotherapy.
EXPERIMENTAL STUDIES
The chondroprotectors glucosamine sulfate (GS) and chondroitin sulfate (CS) show a complex anti-inflammatory effect and therefore may be used in the therapy of many diseases concurrent with osteoarthritis.
Objective: to carry out a systematic analysis of the relationship between the molecular pathophysiology of tenosynovitis and the potential mechanisms of pathogenic action of CS/GS in this disease.
Material and methods. The texts of 15 097 publications were systemized using the current methods for topographic big data analysis, which had been developed as part of topological and metric approaches to recognition/classification problems.
Results and discussion. The investigators created a map showing the molecular pathophysiology of tendosynovitis and including 15 molecular mechanisms and 27 comorbidities and identified mechanisms, through which GS/CS could prevent the development of tenosynovitis, such as inhibition of the effects of proinflammatory cytokines (IL-1, IL-8, γ-interferon, and TNF-α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein, NLRP3 inflammasome, NF-κB and JAK/STAT signaling pathways, and O-glucosamination of proteome proteins. To date, no randomized clinical or cohort (non-interventional) studies of the effects of CS/GS have been conducted in patients with tendosynovitis and comorbidities. However, preclinical studies of GS and CS in the treatment of tendinopathies showed that the drugs had analgesic properties, alleviated chronic inflammation and edema, and improved the maturation of collagen bundles and therefore the mechanical properties of connective tissue in the tendons and ligaments.
Conclusion. The experimental and clinical studies indicate that pharmaceutical-grade GS/CS preparations of high standardization are promising in treating tenosynovitis.
CLINICAL OBSERVATIONS
The described clinical case is unique, since NCM is an extremely rare abnormality, especially when concurrent with Dandy–Walker malformation and an arachnoid cyst. In addition, it is of interest that the manifestation of neurological symptoms and verification of the diagnosis occurred just in adulthood, although NCM is most commonly diagnosed in children.
The present case shows that an operation aimed at improving cerebrospinal fluid dynamics in patients with arachnoid cysts and Dandy–Walker complex in the presence of NCM can lead to a significant reversal of neurological symptoms and improvement in the quality of life despite gross brain structural changes detected by magnetic resonance imaging.
REVIEWS
Citicoline is one of the most widely used nootropic drugs for cerebrovascular pathology. The treatment of VCI involves the prevention of stroke and progressive chronic cerebrovascular disease (CCVD) and the use of drugs improving cognitive functions.
Citicoline is one of the most widely used nootropic drugs for cerebrovascular disease. This drug was synthesized in Japan to treat stroke, then it became widely used in different countries in patients with CCVD and VCI. The data of clinical trials and a Cochrane systematic review prove the efficacy and safety of citicoline in the elderly and senile patients.
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