Vol 48, No 1 (2020)

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A retrospective analysis of the efficacy and tolerability of treatment with everolimus in treatment-refractory epilepsy associated with tuberous sclerosis

Grigoryeva A.V., Dorofeeva M.Y., Perminov V.S., Belousova E.D.


Rationale: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by multiple multi-organ hamartomas. Medically refractory epilepsy (MRE) occurs in up to 60% of TSC patients. The results of the EXIST-3 study have shown the efficacy of MRE treatment with an mTOR inhibitor everolimus. In the Russian Federation, the drug has been approved since 2017 for the treatment of TSC-associated MRE in patients above 2 years of age. Aim: To assess the efficacy of everolimus for treatment of medically refractory seizures associated with TSC. Materials and methods: We retrospectively analyzed medical files from 89 patients with TSC who had been admitted with MRE to the Department of Psychoneurology and Epileptology, Research and Clinical Institute for Pediatrics (Moscow, Russia) from November 2016 to December 2018. The patients were divided into three groups depending on their indications for everolimus: 1) 17 patients received with MRE; 2) 64 patients with MRE and subependymal giant cell astrocytoma (SEGA) of > 1 cm in diameter; 3) 8 patients with MRE and renal angiomyolipoma (AML) of > 3 cm in diameter. Their median age was 7.9 year (range, from 2 to 34 years). There were 45 (50.6%) male and 44 (49.4%) female patients. Their treatment lasted from 6 months to 5 years; the dose of everolimus was 8 mg/m2 . Focal seizures were more prevalent than epileptic spasms: 60 (67.4%) and 29 (32.6%) patients, respectively. Results: There were 9/17 (52.9%) responders in the MRE group, 16/64 (25%) in the MRE + SEGA group, and 4/8 (50%) in the MRE + AML group. Mild to moderate stomatitis was the most frequent side effect (40.5%). Conclusion: Everolimus is a new important agent for MRE in TSC patients. Treatment with everolimus is safe and well tolerated.

Almanac of Clinical Medicine. 2020;48(1):1-6
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Robotic mechanotherapy: the possibility to use an exoskeleton for lower limb rehabilitation in patients with multiple sclerosis and impaired walking function

Gevorkyan A.A., Kotov S.V., Lizhdvoy V.Y.


Background: Robotic mechanotherapy is considered as a promising area of physical rehabilitation of multiple sclerosis patients, while it ensures high training efficacy. Aim: To study the effect of physical training using with the ExoAtlet exoskeleton for lower extremities the functioning of patients with multiple sclerosis. Materials and methods: This was a prospective, open, uncontrolled, single center study. The rehabilitation course with the ExoAtlet exoskeleton included 43 patients (14 male and 29 female, aged from 28 to 59 years, mean age 43,5 ± 9,12 years) with remitting multiple sclerosis in remission (RMS-R) (n = 20) and secondary progressive course (VPRS) (n = 23), with the EDSS scores from 3 to 8. One of the inclusion criteria was the presence of motor paresis of the lower extremities. Training with the ExoAtlet exoskeleton was performed 5 days a week for two weeks. The neurological deficits and functioning were assessed with the Kurtzke expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC) test, including the assessment of walking (Timed 25 Footwalk), of upper limb functions (9-Hole PegTest, 9-HPT), and of mental functioning (Symbol Digit Modalities Test, SDMT) before and after the rehabilitation course. Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) scale. Results: The rehabilitation course resulted in a significant decrease of neurological deficiency by EDSS (by 0.26 score, 5%, p < 0.001). The MSFC test showed an improvement in all subtests: SDMT by 2 points, or 4.9% (p = 0.018), Timed 25-Footwalk by 3.2 seconds, or 19.6% (p < 0.001), 9-HPT for the dominant hand by 1.6 seconds, or 5% (p = 0.004), and for the non-dominant hand by 2.1 seconds, or 6.2% (p = 0.006). The improvement in the MoCA test after the rehabilitation course was 1.6 points, or 6% (p < 0.001). Conclusion: The study confirmed the positive effect of the exoskeleton in the lower extremities, such as restoration of the walking function in multiple sclerosis patients. There was a positive trend towards restoring of hand motor skills and cognitive functions.

Almanac of Clinical Medicine. 2020;48(1):7-12
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Assessment of anxiety and pain in patients with lumbosacral radiculopathy at the early stage of rehabilitation with various rehabilitation programs after microdiscectomy

Blokhina V.N., Melikyan E.G.


Rationale: The role of the psychogenic component in chronic pain and delayed rehabilitation in patients with lumbosacral radiculopathy (LSR) has been extensively studied. However, there is a paucity of studies evaluating anxiety and pain in LSR patients early after microdiscectomy. Only a few studies have performed a differentiated assessment of state (SA) and trait (TA) anxiety. The effects of repetitive peripheral magnetic stimulation (rPMS) on the TA level in the Russian LSR patients have not been investigated. Aim: To assess changes in anxiety and pain over time in LSR patients with various rehabilitation programs at the early stage after microdiscectomy. Materials and methods: The study included 71 patients with LSR after microdiscectomy (mean age 46.8 ± 10.5 years). At Day 7 after surgery, the patients were randomized into two groups. The patients in the 1st group (n = 35) received a rPMS course in addition to conventional rehabilitation, whereas the patients in the 2nd group (n = 36) were rehabilitated only conventionally. Pain was assessed by a visual analogue scale (VAS), and anxiety levels by Spielberger StateTrait Anxiety Inventory (validated Russian version). Results: There was a significant decrease of SA and TA levels in the patients of both groups at Day 21 of rehabilitation, compared to those at Day 7 (p < 0.001). At Day 21, there was a significant inter-group difference (p = 0.036) in the leg pain VAS score and the TA frequency distribution (p = 0.042, Fisher test). Conclusion: Better improvement of pain and trait anxiety in the patients treated with rPMS indicates that it would be reasonable to include an rPMS course into the comprehensive rehabilitation program after microdiscectomy.

Almanac of Clinical Medicine. 2020;48(1):13-21
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The pro-depressive effect of levodopa in a 6-OHDA-induced hemiparkinsonism rat model

Karimova O.S., Morozova A.Y., Zorkina Y.A., Zubkov E.A., Ushakova V.M., Abramova O.V., Chekhonin V.P.


Rationale: Treatment of Parkinson's disease has been by now symptomatic. The literature on the efficacy and side effects of levodopa has been contradictory. Some authors mention an anti-depressant effect of the agent, while others believe that it is exactly levodopa that eventually induces the occurrence of depressive symptoms. Aim: To reproduce the OHDA-hemiparkinsonism rat model with subsequent assessment of both external and structural manifestations of the disorder, as well as to study the efficacy of levodopa for motor and non-motor symptoms of parkinsonism. Materials and methods: The study was performed in 52 male Wistar rats. The disease model included stereotaxic administration of neurotoxic 6-OHDA into the pars compacta of the substantia nigra. At 2 months after the administration, the animals underwent test for motor (Rotarod, cylinder, ketamine-induced rotation in the rotometer) and non-motor abnormalities (open field, social interest, conditioned escape response). Results: In 18% of the animals no hemiparkinsonism symptoms were found. 32% of rats had only motor symptoms, whereas in 50% of the animals both motor and non-motor symptoms were noted. Levodopa could partially correct the motor abnormalities, with augmentation of depressive-like behavior. Conclusion: Levodopa has shown its partial efficacy in correction of the motor symptoms caused by administration of 6-OHDA neurotoxin; however, it caused such side effects as augmentation of depressive-like behavior and anxiety.

Almanac of Clinical Medicine. 2020;48(1):22-33
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Characteristic morphological signs of the brain damage during chronic hepatitis C virus infection identified in autopsy samples

Maybogin A.M.


Background: The central nervous system damage is one of the most common extra hepatic manifestations of chronic hepatitis C viral (HCV) infection, with the prevalence of up to 50% of the infected cases. Previous studies have identified the main clinical, pathogenetic and neurometabolic features of this pathology, which make it possible to suggest its definite nosological independence. However, the morphological pattern of brain lesions in chronic HCV infection remains virtually unexplored, significantly limiting the possibility of comprehensive pathological diagnosis of the disease. Aim: To study morphological patterns and to identify typical and diagnostically significant pathological signs of brain involvement in chronic HCV infection. Materials and methods: This was a retrospective descriptive cross-sectional study performed with a range of immunohistochemical (IHC) and pathomorphological techniques in the autopsy brain samples from patients who died of chronic HCV infection (40 cases) and those who died without any signs of past mental and infectious disorders (the control group, 15 cases). Results: The сharacteristic morphological signs of HCV-associated brain injury are IHC expression of the NS3 viral marker, an increase in CD68-positive microglial cell count, white brain matter microgliosis, perivascular and diffuse round cell inflammatory infiltration, degeneration and loss of neurons, neurophagy, demyelination, axonal degeneration, perivascular sclerosis, fibrous cell gliosis, small perivascular hemorrhages, focal hemosiderosis and calcification. The parameters of the identified abnormalities differ significantly depending on the brain region (p < 0.001). The identification of the HCV NS3 marker in the nervous tissue has the definitive diagnostic value. Conclusion: The body of histopathological abnormalities found in various parts of the brain from the infected patients represents the morphological equivalent of the clinical and functional manifestations of HCV-associated cerebral dysfunction. The results obtained can be used to improve the pathological diagnostics of brain lesions in chronic HCV infection; their implementation is feasible in routine pathological practice.

Almanac of Clinical Medicine. 2020;48(1):34-43
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The relationship of sleep mechanisms and epileptogenesis

Kozhokaru A.B., Vlasov P.N., Orlova A.S.


Close links between epilepsy and sleep is doubtless; however, the available literature does not allow for its unequivocal interpretation from the common pathophysiological mechanisms' perspective. GABAergic neuronal deficiency is believed to be the neurochemical background of the intimate mechanisms of sleep and epileptogenesis. Sleep impacts the epileptiform activity, with an increase in epileptiform discharge during NREM and a decrease during REM phases. Sleep deprivation may complicate the course of epilepsy, while epileptic attacks may change the sleep structure and quality. Anti-epileptic agents exert diverse effects on the sleep architectonics; they can induce sedation or increase alertness. Our potential to correct the results of the pathological interplay between sleep mechanisms and epilepsy are rather limited and are frequently overestimated by clinicians. Investigation of the interrelationship between epileptic seizures and sleep and the use of polysomnography can substantially add to the diagnosis of the epileptic syndrome and define the subsequent outcomes.
Almanac of Clinical Medicine. 2020;48(1):44-55
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Clinical heterogeneity of chronic inflammatory demyelinating polyneuropathy: diagnostic challenges

Rizvanova A.S., Grishina D.A., Suponeva N.A.


Сhronic inflammatory demyelinating polyneuropathy (CIDP) is the most prevalent acquired dysimmune neuropathy with clinical picture of symmetric motor and sensory disturbances. Since the first description of CIDP, many atypical variants have been described, which may reach up to 50% of cases. Diagnosis of atypical CIDP may be challenging due to different clinical presentation and treatment response. Current researches improve our knowledge about dysimmune neuropathies and highlight the importance of its classification. Nowadays CIDP is considered as a spectrum of disorders rather than a separate disease entity. Up to date, more than 15 diagnostic criteria have been proposed reflecting the complexity of СIDP diagnosis. Many polyneuropathies may mimic CIDP, therefore CIDP is frequently a diagnosis of exclusion. The key diagnostic instrument is electroneuromyography; however, the issues related to results misinterpretation and some technical aspects are the most important in CIDP misdiagnosis. Supportive instrumental and laboratory methods have variable sensitivity and specificity, making challenging CIDP diagnosis, especially its atypical forms. The importance of an early and accurate diagnosis of CIDP is supported by an effective pathogenic treatment, which affects the patient's prognosis and level of disability.
Almanac of Clinical Medicine. 2020;48(1):56-64
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To solve the problem of driving a car in epilepsy: by liberalization or by tightening the license?

Ponomareva I.V., Gerzen A.P., Lapina M.N., Sherman M.A.


In the modern mobile world, there is no single solution to the problem of issuing a driving license for patients with epilepsy. Most countries do have liberalized laws that allow driving a car to persons with controlled epilepsy. As far as individuals with regular seizures are concerned, there is a temporary prohibition to drive with potential restoration of the driving right if there is no relapse. The existing experience has shown that such strategy can lead not only to higher quality of life of the patients (more than 70% patients with epilepsy has the right to drive a car), but also to ensure the road safety. Even with this quite liberal approach, about 20% of the drivers with epilepsy do not have their epilepsy fully controlled. In the countries with absolute prohibition of the driving in epilepsy, such as the Russian Federation and China, there is no official statistics on the issue. Based on our practical experience, we concluded on a high (at least 35%) prevalence of drivers among patients with epilepsy; this cannot but increase the risk of road accidents, including fatal. Based on a clinical observation, we illustrate the failure of the mechanisms to prevent road accidents related to epilepsy that are currently in force in the Russian Federation. In our opinion, the problem under discussion does not have an exclusively medical solution. Taking into consideration the accumulated world experience, ensuring of the road safety requires that the state law regulations should be in effect that include a differentiated approached to issuing of permissions to drive a car for persons with epilepsy, from one side, and a serious legal treatment of persons with epilepsy who ignore their adequate therapy and become a cause for road accidents inflicting an injury, from the other.
Almanac of Clinical Medicine. 2020;48(1):65-72
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Comment on "To solve the problem of driving a car in epilepsy: by liberalization or by tightening the license?"

Belova Y.A.


Almanac of Clinical Medicine. 2020;48(1):73-74
pages 73-74 views

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