LECTURES
The presence of indications for long-term oral anticoagulant (OAC) therapy in a patient who has experienced an intracerebral hemorrhage (IUD) poses a difficult clinical dilemma for the physician. The article discusses the vectors of recurrence for different types of IUD and their neuroimaging markers. It describes approaches to the global assessment of risk factors for IUD in patients taking OACs. Detailed consideration is given to the situation of IUD concurrent with atrial fibrillation as the most common reason for prescribing OACs. There are data on the safety of restating OACs after IUD and on the risk of the latter in patients taking warfarin and direct OACs. The optimal OAC start or restart time after IUD, including that in patients with prosthetic valves, is discussed. An algorithm for decision making is recommended.
Many classes of medications, such as antipsychotics, anticonvulsants, anticholinergics, and other commonly prescribed drugs, can cause cognitive impairment (CI). The negative effect of drugs on cognitive functions is due to the following pathophysiological mechanisms: a reduction in neuronal excitability, an increase in gamma-aminobutyric acid activity, and decreases in enzyme activity, the number of receptors, cerebral perfusion, as well as brain atrophy; moreover, a number of mechanisms have not been fully studied. An important role in the development of drug-induced CI is played by predisposing (senility or childhood, brain damage, chronic diseases, functional disorders, genetic causes, initial cognitive decline, polypragmasia), and precipitating (acute diseases, infections, metabolic disorders, dehydration, acute urinary retention, malnutrition, environmental influences, etc.) factors. The dose of a drug, the duration of its use is of absolute value. There is a need for the differential diagnosis of CI induced by drugs and CI directly related to the diseases, for which these drugs are prescribed. Drug-induced CI should be suspected if an association is established between a decline of cognitive functions and the start of drug intake. The treatment of this CI involves primarily dose withdrawal or reduction and the use of sustained-release dosage forms, if available. In some cases, cognitive training and/or special drug therapy may be required to correct the CI that has occurred. The measures to prevent drug-induced KI include the choice of the lowest-risk drugs, the use of current side-effect rating scales, in particular an anticholinergic burden scale.
ORIGINAL INVESTIGATIONS
Post-stroke spasticity (PS) occurs in most patients with stroke and contributes to the development of pain syndrome and contractures, which substantially impairs the restoration of lost motor functions (MFs) and the quality of life of the patient.
Objective: to evaluate the efficacy of a combination of botulinum toxin A (BTA) and multimodal stimulation in patients with arm PS.
Patients and methods. The investigation enrolled 84 patients aged 18 to 85 years with PS, who had experienced ischemic stroke (IS) 1 month to 1 year before. In the study group (n=56), complex rehabilitation treatment was preceded by the use of BTA, while in the control group (n=28), multimodal rehabilitation therapy was performed without using BTA. Before and after treatment, neurological deficit was evaluated using the modified Ashworth scale (MAS), the Fugl—Meyer (FM) assessment scale, the British muscle strength grading scale, the Action Research Arm Test (ARAT), the Barthel index, and the modified Rankin scale.
Results and discussion. According to MAS, there was a statistically significantly spasticity reduction after BTA use in the study group compared to the control one (median 1 [1; 2] and 2 [2; 3] scores, respectively; p=0.0003). According to the FM scale, an improvement in arm MFs was noted in the study group compared to the control one (median 29.5 [20; 42] and 21 [13.5; 31.5] scores, respectively; p=0.008) and according to the ARAT scale this was observed in the study and control groups (14.5 [7; 27] and 3 [0; 12] scores, respectively; p=0.0004).
In patients with upper limb PS, the use of BTA before a rehabilitation cycle using multimodal stimulation was shown to be statistically significantly more effective than the similar neurorehabilitation cycles without prior BTA therapy. The findings can be used in the routine practice of a neurologist when planning rehabilitation for more effective and well-founded treatment in patients with arm PS.
Conclusion. Incorporation of BTA into multimodal stimulation was ascertained to be effective in patients with PS.
Chronic inflammatory demyelinating polyneuropathy (CIDP) in patients with diabetes mellitus (DM) occurs approximately 9—11 times more frequently than in the general population.
Objective: to assess the characteristics of CIDP in the presence of DM.
Patients and methods. A total of 109 patients with CIDP diagnosed according to the international EFNS/PNS criteria were examined. Seventeen patients had type 1 or 2 DM; the remaining 92 patients did not.
Results and discussion. The patients with CIDP and DM were found to have significantly more obvious neurological deficit, lower levels of selfservice, and a shorter time to diagnose CIDP than those with CIDP without DM.
The concurrence of CIDP and DM is ambiguously assessed. On the one hand, there are indications of a strict correlation between these conditions, and on the other, the absence of this association. Our study showed that more obvious neurological deficit in DM can be related to the additional damaging impact of chronic hyperglycemia as impaired metabolism of nerve fibers and deterioration of their trophism. The autoimmune nerve damage occurring in CIDP is superimposed on the already existing impairments in the microcirculation and dysfunction of peripheral nerves, thereby increasing their damage.
Conclusion. The course of CIDP in the presence of DM differs from that of «pure» CIDP, which should be taken into account in managing these patients.
Myelopathy occurs in 1% of patients with sarcoidosis and is usually caused by the underlying disease. Comorbidity as its possible cause should be excluded, especially in a case of atypical neurosarcoidosis.
Objective: to analyze the features of myelopathy in patients with systemic sarcoidosis
Patients and methods. Twelve patients (7 women and 5 men) aged 41.5 [32.5; 45.3] years with systemic sarcoidosis and myelopathy were examined. The clinical and radiographic features of spinal cord (SC) injury and the nature of changes in laboratory parameters were analyzed.
Results and discussion. The cause of myelopathy was sarcoidosis (neurosarcoidosis (NS)) in 7 (58%) patients (Group 1) and multiple sclerosis in 4 (33%) (Group 2). One more patient developed myopathy due to extradural lipomatosis (this case is described in the clinical observation section). In Group 1, myelopathy was the first manifestation of sarcoidosis in 4 (57%) of the 7 patients. Six (86%) patients were observed to have incomplete regression of symptoms; 5 (71%) showed a progressive course. Magnetic resonance imaging (MRI) revealed the signs of a lesion in the thoracic SC in 4 (57%) patients with NS, as well as damage to three or more of its segments in 5 (71%) and a radiological pattern of sarcoidosis-induced SC lesion in 6 (86%). MRI findings showed that all the 4 (100%) patients in Group 2 had cervical SC injury, no patterns typical of NS, as well as the signs of meningeal contrast agent accumulation. None of them displayed pleocytosis and low glucose levels in the cerebrospinal fluid. Extradural lipomatosis-induced myelopathy was compressive with positive changes after discontinuation of glucocorticoids.
Conclusion. It is necessary to take into account the possibility of comorbidity as a cause of myelopathy in patients with sarcoidosis and the likelihood of SC lesion as a complication of therapy for the underlying disease.
Objective: to investigate the features of the pathogenesis, diagnosis, and treatment of panic attacks (PAs) in young people.
Patients and methods. A total of 39 outpatients (27 females and 12 males) aged 19 to 38 years with PAs were examined. The Panic Disorder Severity Scale (PDSS) was used to measure the severity of clinical manifestations of PAs; the Covey Anxiety Scale was employed to identify an anxiety state. In order to exclude depressed patients from being examined, the Montgomery—Аsberg rating scale was applied to assess the severity of depression. All the patients were divided into two groups: 1) 22 patients with PAs who received standard therapy and the alpha-adrenoblocker proroxan (Vegetrox) as a 15-mg tablet thrice daily for 8 weeks; 2) 17 patients who were prescribed only standard therapy. The patients were examined twice before and 4 weeks after the end of an 8-week vegetrox therapy cycle.
Results and discussion. In the patients of both groups with PAs, the total score ranged from 3 to 11, with the median PDSS score of 7. According to the Covey anxiety scale, an anxiety state developed in 33 patients; only the symptoms of anxiety were detected in 6. There was a direct significant correlation between the PDSS and Covey anxiety scale values; Spearman's rank correlation coefficient was 0.681 (p<0.01). The PA severity indexes proved to be significantly lower after incorporating Vegetrox into the standard therapy. Comparing the anxiety scale values in the patients of Groups 1 and 2 after the treatment cycle revealed a significant decrease in the level of anxiety in the patients receiving standard therapy and Vegetrox. This effect of the latter may be explained by the fact that it blocks postsynaptic α1-adrenoceptors and presynaptic α2-adrenoceptors and decreases the stimulation intensity of the hypothalamic structures that are closely connected with the limbicoreticular system.
Conclusion. The severity of PAs in young people depends on the level of anxiety. Vegetrox has a significant positive effect on the values of PDSS and the Covey anxiety scale in PAs.
Diabetes mellitus (DM) is a metabolic disease that is accompanied by brain injury manifested as cognitive impairment (CI).
Objective: to study cerebral structural and functional changes in patients with DM according to the presence of CI.
Patients and methods. Examinations were made in 60 patients with type 1 DM and 60 with type 2 DM who were divided into groups according to the presence of CI. The Montreal Cognitive Assessment (MoCA test) was used to evaluate CI. Glycemia and its variability and the level of glycated hemoglobin (HbA1c) were analyzed. MRI brain images were segmented using the FreeSurfer program and the Recon-all software package. Brain functional MRI was performed using paradigms (for Broca's, Wernicke's and primary motor areas).
Results and discussion. Patients with type 1 DM and CI were found to have reduced volumes of the entire white matter and the right hippocampus; those with type 2 DM had decreased gray and white matter volumes. The functional activities of the primary motor and Broca's areas were reduced by 50% in patients with types 1 and by 80% in those with type 2 when conducting the tasks. A relationship was established between disease duration, patient age, glycemic variability index, MoCA test results, and decreases in the volumes of the hippocampus and white and gray matter and in the activity of motor areas in types 1 and 2 DM.
Conclusion. Gray and white matter atrophy and impaired motor area functional activity are more significant in type 2 DM. These changes are associated with CI and glycemic variability.
Objective: to retrospectively assess the Russian experience with perampanel (PER) in everyday clinical practice as an adjunctive medication for the treatment of patients aged 12 years or older with focal epilepsy (FE).
Patients and methods. A multicenter retrospective study was conducted, during which the physicians filled out standard questionnaires assessing the characteristics of the disease and the therapy performed. The maximum follow-up period was 12 months. Each patient was included in the study only once for the duration of the study. A total of 164 cases of pharmacoresistant FE were analyzed. The patients' mean age was 37.7 years; the male to female ratio was 1:1. The disease duration over 10 years was in 68.7% of patients; structural epilepsy was present in 68.2% (temporal and frontal lesions in 53.4 and 39.1%, respectively)
Results and discussion. Most (26.6%) patients were prescribed PER after three previous lines of therapy; before PEP administration, there was a maximum of 2 (50.9%) and 3 (29.6%) drugs, respectively, in the combination. The initial frequency of all seizure types reached 9 [3; 34] per month; that of focal-onset bilateral tonic-clonic seizures was 3 [2; 6] per month. Combined therapy including PER could lead to the disappearance of seizures in 22.7% of cases; the responders (by all seizure types) were 52.8%, whereas the remission rate of bilateral tonic-clonic seizures was 60.8% of patients, the responder rate was 27,8%. At 12 months of follow-up, the therapy retention rate reached 80.7% (95% confidence interval, 72.3—89.1). Adverse events (AEs) were noted in 31.3% of patients; the most frequent AEs were drowsiness (10.4%), aggression (9.8%), irritability (6.7%); other AEs were observed in individual cases. The average dose of PER was 8 mg.
Conclusion. PER was effective in patients with resistant PEs at a maximum follow-up of 12 months in routine clinical practice. Remission of all seizure types was achieved in 22.7% of cases, the decrease in the number of seizures >50% was seen in 52.8% of cases; the therapy retention rate was 80.7%. The drug had a therapeutic effect in all types of focal seizures and was most effective in focal-onset bilateral tonic-clonic seizures. Along with its good clinical effect, PER demonstrated a predictable safety profile.
Lacosamide (LCM) is one of the most promising antiepileptic drugs (AEDs) for focal epilepsy (FE); however, in Russia there are only a few works devoted to its practical application.
Objective: to evaluate the efficiency of LCM therapy in adolescents and adults with new-onset FE.
Patients and methods. The investigation enrolled 36 patients aged 16-78 years. All the patients underwent video-ECG monitoring with quantification of the epileptiform activity index (EAI) at baseline and 1, 3, 6 and 12 months of treatment. The treatment efficiency was evaluated using the standard measures: drug-induced remission, a response rate of ≥50%, an insufficient efficiency of ≤50%, higher seizure frequency, and therapy retention rates. Adverse events (AEs) were assessed using the SIDe-effects of AntiEpileptic Drugs (SIDAED) questionnaire.
Results and discussion. Just 3 months after starting treatment, the total EAI substantially decreased from 2.92 [0; 6.7] to 1.95 [0; 3.07] (p<0.05). LCM demonstrated a high efficacy and a good tolerance in the therapy of FE: by the end of 12-month follow-up, there was a considerable decrease in EAI by 1.57 times (p<0.05); the LCM monotherapy retention rate of 72.2% was achieved in 26 patients: 20 (55.6%) patients had drug-induced remission; six (16.7%) patients were responders. AEs were recorded in 5 (13.8%) cases.
Conclusion. LCM is an effective AED for the initial monotherapy of FE. The use of LCM in FE causes a considerable decrease in EAI by 1.57 times (p<0.05).
Recent systematic reviews and a meta-analysis have shown that there is insufficient evidence on the relationship of multiple sclerosis (MS) to vitamin D supplementation
Objective: to assess the relationship of vitamin D status in MS patients to insolation, disease course, and HLA-DRB1 gene polymorphism. Patients and methods. The one-stage study enrolled 90 patients with relapsing-remitting MS (a study group) and 87 volunteers without this disease (a control group). The enrolled were born and live in the Altai Territory of the Russian Federation. The serum level of 25(OH)D was measured by enzyme immunoassay.
Results and discussion. 25(OH)D <30 ng/ml was more common in patients with MS than that in the controls. There were no intergroup differences in the time spent in the sun for 6 months before inclusion in the study (p=0.020). The level of 25(OH)D was higher in the high insolation period from April to September than that in the low insolation period from October to March in both patients with MS (p<0.005) and controls (p<0.001). There was no association of 25(OH)D levels with urban and rural residence, gender, age at MS onset, severity of neurological disorders, their progression rate, and MS risk alleles within the HLA-DRB1 gene (03, 13, 15).
Conclusion. Vitamin D deficiency is more common in patients with MS than in those without this disease. This is unlikely to be due to the differences in the radiation received from the sun. The final conclusion on the relationship of vitamin D to MS can be made after obtaining the results of a prospective follow-up.
Cervical dystonia (CD) is manifested by violent, often painful movements of the neck muscles with the abnormal head and/or neck postures being formed. Disease progression leads to disability of patients. The clinical picture of the disease is characterized by a concurrence of motor and non-motor disorders.
Objective: to analyze the features of non-motor manifestations (pain, asthenia, anxiety, depression, sleep disorders) and quality of life (QOL) in patients with CD.
Patients and methods. A total of110 patients (31 men and 89 women) aged 27—82years (mean age, 54.4±12.4 years) with CD (a study group) were examined. A control group consisted of 50 patients (16 men and 34 women) aged 25—82 years (mean age, 51.7±14.8 years) with cervical dorsalgia. Clinical, neurological, and neuropsychological examinations were made according to validated questionnaires. The investigators assessed pain using a visual analogue scale, anxiety and depressive disorders by the Hospital Anxiety and Depression Scale (HADS), asthenia by the Multidimensional Fatigue Inventory (MFI-20) and the scale of asthenic state (SAS), night sleep quality by the Pittsburg Sleep Quality Index (PSQI), and quality of life by the 36-Item Short Form Survey (SF-36).
Results and discussion. The patients with CD showed a high incidence ofnon-motor disturbances: pain (98%), asthenia (90%), nocturnal sleep disorders (80%), anxiety (53%), and depression (48%). Non-motor symptoms were statistically significantly more obvious in the patients with CD than in those with cervical dorsalgia. The QOL indicators in CD were statistically significantly reduced in all physical and psychological parameters.
Conclusion. Non-motor manifestations occupy an important place in the clinical picture of CD, substantially reducing the physical and psychological aspects of QOL in the patients.
Standard treatment for lower back pain (LBP) includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
Objective: to determine the magnitude of the effect of injectable chondroitin sulfate (CS) as part of combination therapy for LBP on the intensity of pain syndrome.
Patients and methods. The investigation was conducted in August 2019 to February 2020. A total of 60 patients (23 men and 37 women) aged 36 to 66 years (mean age, 48.65±8.72 years) with non-specific LBP were followed up. The patients were divided into two equal groups. A study group (n=30) took a NSAID (meloxicam) 7.5 mg twice daily for 7—10 days and intramuscular (i.m.) CS every other day in accordance with the scheme: the first three injections at a dose of 1 ml (100 mg) on days 1, 3, and 5; if this was well tolerable, a dose of 2 ml (200 mg) from the 4th injection (on day 7). A control group (n=30) used meloxicam 7.5 mg twice daily for 7—10 days. Changes in the patients' status were evaluated at baseline and 10, 20, and 50 days after therapy. The authors used a numerical rating scale (NRS) to determine the intensity of pain (at rest, during walking, during palpation), as well as the Oswestry functional status scale (OFSS). Adverse events (AEs) were evaluated.
Results and discussion. In the study group, there was a decreased need for NSAIDs on day 7 of therapy, whereas in the control group, there were no dosage regimen changes through the treatment cycle. The intensity of pain syndrome according to the NRS decreased by 89.8% in the study group and by 68.3% in the control group; that according to OFSS reduced by 95.5% in the study group and by 86.6% in the control group (p<0.05). The use of i.m. CS injections in the combination therapy of LBP increases the efficiency of treatment, can reduce the dose of NSAIDs and improve the functional capabilities of the patients with pain syndrome. The safety of CS was confirmed by the absence of AEs throughout the follow-up period.
Conclusion. The investigation has demonstrated that the use of i.m. CS injections in the combination therapy of LBP can improve treatment outcomes.
On March 11, 2020, the WHO announced the COVID-19 outbreak a pandemic. The disease was established to be caused by a new singlestranded RNA virus (ss-RNA, 29903 bp) that belongs to a group of coronaviruses (CoV).
Objective: to assess the results of a pilot analysis of the efficiency of using Angiovit in the combination treatment of acute COVID-19 with pneumonia or acute respiratory viral infection.
Patients and methods. The study enrolled 50 patients with acute COVID-19. In all the patients, the diagnosis of coronavirus infection was confirmed by polymerase chain reaction. Angiovit was used in 25 patients (13 (52%) women) (mean age, 39.4 years) with moderate infection who had been admitted on an average of disease day 3 (a study group). A comparison group consisted of 25 patients whose gender, age, and clinical features of COVID-19 did not differ at the time of admission; they were prescribed only mainstay therapy.
Results and discussion. Adding Angiovit to the mainstay therapy contributed to an average reduction in the fever period from 5.88 to 4.12 days (p<0.05) and to the earlier hospital discharge of patients with an improvement (on day 13 versus on day 16.8 days in the comparison group; p<0.05); Normalization of CRP, D-dimer, and homocysteine levels occurred considerably and faster.
Conclusion. The pilot study has shown that the use of Angiovit in the combination therapy of COVID-19 reduces the clinical and laboratory manifestations of inflammation and hypercoagulation, which may also be associated with the action of folic acid.
CLINICAL OBSERVATIONS
There is now increasing evidence that demyelinating disease with anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies is an independent nosological unit. The paper describes a clinical case of anti-MOG associated myelitis at the CI-TXlevel. Differential diagnosis was made between multiple sclerosis, Devic's myelitis optica, and idiopathic transverse myelitis. The clinical, morphopathological, and diagnostic features of anti-MOG associated myelitis are discussed. There are new diagnostic criteria for neuromyelitis optica spectrum diseases (NMOSD), as well as red flags, in the absence of which the diagnosis of NMOSD can be established as a diagnosis of exclusion.
PHARMACOTHERAPY
Currently, special attention is paid to timely treatment for active forms of multiple sclerosis (MS), especially for highly active MS (HAMS), in which there are ≥2 exacerbations and corresponding activity signs that are detected by magnetic resonance imaging (MRI) regardless of previous therapy with MS-modifying drugs (MSMDs) or there is ≥1 exacerbation and corresponding activity signs revealed by MRI during therapy with other MSMDs. A group of expert neurologists from various clinics in Russia, who actively participate in the clinical trials of cladribine tablets in MS, presents a consensus on the practical aspects of using the tablets of cladribine registered in Russia in March 2020 for the treatment of patients with HAMS. The paper mentions the groups of patients in whom the drug, an examination before starting a therapy cycle, routes of administration, and dose, and a monitoring scheme during and after treatment cycles are indicated. This drug acts on the principle of selective immunoreconstitution and may occupy an important place in the treatment of HAMS.
REVIEWS
This review considers obstructive sleep apnea syndrome (OSAS), one of the common causes of insomnia. It is indicated that not only the population, but also the physicians are often unaware of treatment and prevention options for this disease. The review characterizes OSAS treatment that includes different approaches. It demonstrates the results of studies on the efficiency of continuous positive airway pressure (CPAP) therapy. The review describes approaches to identifying, monitoring, and treating sleep disorders, as well as proposals regarding the effective prevention of OSAS. It notes the important role of drivers' observation of working and resting conditions and a healthy lifestyle, as well as the need to follow up patients with OSAS in order to reduce the number of traffic accidents.
Atrial fibrillation (AF) is a common rhythm disorder, especially in the elderly and senile people, and its incidence is expected to be only increasing. Another urgent problem of modern health care is cognitive impairment (CI) and dementia, which are also highly prevalent. Studies show that AF and CI are closely interrelated: patients with this heart rhythm disturbance are at increased risk for both CI in general and dementia in particular, their cognitive decline progresses faster regardless of whether AF is paroxysmal or permanent. The association between CI and AF is largely due to the commonality of risk factors, the main of which are considered to be elevated blood pressure, atherosclerotic vascular damage, diabetes mellitus, and age. To date, the specific pathogenetic mechanisms of CI development in AF have been described, indicating that both vascular and neurodegenerative changes are implicated in cognitive decline in the presence of cardiac arrhythmias in question. These changes include a history of stroke, the well-known risk factor for the cardioembolic type of which is AF; microembolism and microhemorrhage; predisposition to prothrombotic states; cerebral hypoperfusion and a proinflammatory shift associated with this arrhythmia. In addition, a potential adverse effect on CI can be produced by the use of antagonists of vitamin K, since the latter is an important trophic factor necessary for normal cognitive functioning.
Cognitive impairment (CI) and distal polyneuropathy are the most common neurological complications of diabetes mellitus (DM) and depend not only on the severity and duration of hyperglycemia, but also on the presence of concomitant diseases. Patients with DM have one or more concomitant diseases that deteriorate the course of each other, and their joint correction improves the patient's status and quality of life. Management of DM patients requires a multidisciplinary approach at the time of diagnosis in order to prevent and identify major complications, to optimize drug therapy, and to use non-pharmacological treatments.
According to the instruction approved in the Russian Federation, Akatinol Memantine is indicated for the treatment of all types of dementia regardless of its severity. In addition, data are being accumulated on the use of memantine in a wide range of mental disorders, including schizophrenia, bipolar affective disorder, recurrent depression, obsessive-compulsive disorder, etc.
This review is devoted to the analysis of an update on adjuvant therapy with memantine for the above mental disorders. It discusses the precogni-tive and antinegative effects of the drug in schizophrenia on the basis of the data of meta-analyses and double-blind, placebo-controlled studies.
The review sets out modern ideas about the mechanisms of action of gamma-aminobutyric acid (GABA) in the central nervous system and other organs and systems. Current experimental and clinical studies have shown that GABA has numerous effects: neuroprotective, antihypertensive, antidiabetic, antitumor, anti-inflammatory, antimicrobial, anti-allergic, hepatoprotective, nephroprotective and enteroprotective, and others, which are currently the subject for study by biologists, physiologists, and physicians. Synthetic GABA analogues are widely used in clinical practice. One of these drugs is aminophenylbutyric acid hydrochloride (Anvifen®) that has demonstrated high efficiency and safety in clinical practice.
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