Vol 7, No 2 (2013)

Original articles

The role of cyclosporin in the treatment of severe myasthenia: a clinical study of 51 patients

Shcherbakova N.I., Pavlova E.М., Lantsova V.B., Savitskaya N.G., Pavlov E.V., Retinskaya I.G., Zakutnaya V.N.

Abstract

About 15–20% of myasthenic patients are refractory to standard steroid therapy. The present study was aimed at evaluation of efficacy and analysis of the algorithm of use of a novel immunosuppressant of natural origin, cyclosporine A, in the treatment of severe refractory forms of myasthenia gravis. In this work, for the first time on a large group of myasthenic patients (51 patients who became ill at 5–80 years of age), mechanisms of action of cyclosporine (sandimmun orally 2.5–5 mg/kg) on main levels of neuro-muscular junction were studied, and new confirmation of selective immune-modulating activity of cyclosporine (without total decrease of patient’s immune system) was presented. High efficacy and good tolerability of the drug in different pathogenic subtypes of myasthenia gravis were shown. Cyclosporin may be recommended in refractory steroid-dependent myasthenia, as well as in cases of combination of myasthenia with thymoma, autoimmune disorders and immunodeficiency viral infections.

 
Annals of Clinical and Experimental Neurology. 2013;7(2):4-10
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Robot-assisted therapy with the use of MOTOmed letto 2 in complex early rehabilitation of patients with stroke admitted to the intensive care unit

Prokazova P.R., Piradov M.A., Ryabinkina Y.V., Kunzevich G.I., Gnedovskaya E.V., Popova L.A.

Abstract

Objective: to assess the effect of early robot-assisted rehabilitation (MOTOmed Letto 2) on neurological recovery, severity of the disease, the rate and severity of multiple organ dysfunction syndrome and the rate of venous thromboembolism in acute stroke patients during intensive care unit (ICU) stay, including patients who require mechanical ventilation. This case-control study included 66 patients (49 males and 17 females, median age 59) with acute ischemic stroke and cerebral hemorrhage admitted to ICU. Patients were distributed into two comparable groups, intervention (n=33) and control group (n=33), and monitored from admission to day 21. Both groups received standard rehabilitation from admission, and patients in the intervention group also received robot-assisted arm and leg therapy. Groups had similar median GCS, NIHSS, APACHE II, MODS scores on admission. There was no significant difference in neurological and medical outcome on day 21 (median GCS: 15 vs. 15, p=0.32; median NIHSS 11 vs. 15, p>0.05; median APACHE II 6 vs. 9, p >0.05; median MODS 0 vs. 1, p >0.05 in the intervention and control group, respectively). The rate of multiple organ dysfunction syndrome and deep venous thrombosis (DVT) on day 21 was also similar in the intervention and control groups (60% vs. 67%, p>0.05, and 57.6% vs. 45.4%, p>0.05, respectively). The rate of severe multiple organ dysfunction syndrome, incidence of pulmonic embolism (PE) and mortality rate were lower in the intervention group vs. control group (14%, vs. 41%, p<0.05; 12% vs. 33%; p<0.05; 12% vs. 39%, p<0.05, respectively). Early robotassisted therapy in patients with severe stroke admitted to the ICU was associated with significant reduction of PE rate, incidence of severe multiple organ dysfunction syndrome and mortality on day 21, but did not influence neurological outcome and DVT rate.

Annals of Clinical and Experimental Neurology. 2013;7(2):11-15
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Glutamate excitotoxicity in multiple sclerosis

Ryazantseva A.A., Alifirova V.M., Ivanova S.A., Boyko A.S., Krotenko N.M.

Abstract

A comparative analysis of the level of neuroactive amino acid glutamate in the blood serum of 17 healthy individuals and 63 patients with multiple sclerosis (MS), according to the course, stage and duration of the disease and disability, was performed. The level of glutamate was significantly higher in MS patients (16.47±4.37 nmol/μl) compared to healthy individuals (11.31±3.08 nmol/μl). It was increased by 43.4% in relapsing-remitting type of MS, by 45.3% in secondary progressive MS, and by 66.3% in primary progressive MS. In exacerbation of the disease, glutamate concentration reached maximum values (18.44±3.44 nmol/μl) compared to remission (15.12±3.97 nmol/μl). No significant changes in the levels of glutamate depending on the duration of illness and severity of disability were found. The obtained results can be used as one of additional diagnostic criteria for determining the disease stage, and control over the level of glutamate may become a new therapeutic target in MS.

 
Annals of Clinical and Experimental Neurology. 2013;7(2):16-19
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Transcranial magnetic stimulation in complex therapy of epilepsy

Evstigneev V.V., Kisten' O.V.

Abstract

Analysis of clinical, electroencephalographic and neuroimaging data of 19 patients with epilepsy after a course of repetitive transcranial magnetic stimulation (rTMS) in combination with subtherapeutic doses of anticonvulsants was performed. It was found that 1 Hz low-frequency temporal rTMS combined with anticonvulsants helps to reduce the number of weekly seizures by 91.9% during the course of this procedure, and by 75% during the month after completion of the combined course. rTMS courses lead to reduction of interictal epileptiform activity and decrease in the number of patients with pathological epileptic EEG phenomena, which may be seen not only in the stimulation period, but also during the following 4–12 weeks. rTMS has the long lasting effects on EEG parameters: increase in the alpharhythm power with frequency-spatial structure improvement, and decrease in the theta-rhythm and pathological beta-rhythm with minimization of the number and size of their focuses. The use of low-frequency and low-intensity rTMS together with subtherapeutic doses of anticonvulsants allows avoiding the development
of side effects and ensuring high anti-seizure activity

Annals of Clinical and Experimental Neurology. 2013;7(2):20-26
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Citicoline in the prevention of postoperative cognitive dysfunction during total intravenous anesthesia

Ovezov A.M., Lobov M.A., Nad’kina E.D., Myatchin P.S., Panteleeva M.V., Knyazev A.V.

Abstract

At present there is strong evidence of negative influence of general anesthesia on the brain, with the development of postoperative cognitive dysfunction (POCD). The lack of generally accepted approaches to medicamentous prevention of POCD raises the question of intraoperative cerebral protection. Forty female patients (aged 17–69 years) who underwent laparoscopic cholecystectomy under total intravenous anesthesia (TIVA) based on propofol and fentanyl were included in the randomized double-blind placebo-controlled study. Twenty patients were
randomly assigned to the main group and were given intraoperatively citicoline (Ceraxon, 1000 mg i.v.), and 20 patients received placebo. Hemodynamics, Harvard standard of patient’s safety, bispectral and perfusion indexes were intraoperatively monitored. Neuropsychological testing including tables of Schulte, the 10 words recall test and the Hospital Anxiety and Depression Scale (HADS) were performed preoperatively, as well as on day 1 and day 3 after surgery. Both groups were matched by demographics, coexisting pathology, preoperative cognitive status and anxiety. Anesthesia was adequate with equivalent demand of anesthetics in all patients. Post-anesthesia
recovery period parameters were significantly better in the treatment group compared to placebo (p<0.05). On day 1, POCD was detected in 20% of patients in the treatment group and in 50% in the placebo group (p<0.05). On day 3, improvement of long-term memory (by 56%) and attention (by 14.3%) was observed in the Ceraxon group comparing to placebo (p<0.05). HADS results on day 1 did not show any significant difference between the groups, but a positive trend of the decrease of anxiety in the treatment group was observed. Thus, Ceraxon used
intraoperatively does not influence on anesthetic consumption, significantly improves the course of postanesthetic recovery and prevents the development of POCD in the postoperative period

Annals of Clinical and Experimental Neurology. 2013;7(2):27-33
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Brain nigrostriatal system changes in rotenone-induced parkinsonism (quantitative immune-morphological study)

Voronkov D.N., Dikalova Y.V., Khudoerkov R.M., Yamshchikova N.G.

Abstract

For studying one of the commonest diseases of the nervous system, parkinsonism, long-term course of injections of pesticide rotenone to Wistar rats was used, and thereafter changes of neurons and glial cells in the nigrostriatal regions of the brain were investigated by immunohistochemical methods. It was found that rats treated by rotenone were characterized by reduced motor activity and displayed characteristics of experimental parkinsonism. These changes were accompanied by a decreased tyrosine hydroxylase staining in the processes of the s. nigra dopamine neurons and aggregation of α-synuclein in their bodies, as well as by significant loss of dopamine cells in the rostral part of the s.nigra. Rotenone produced bilateral local destruction of brain tissue with surrounding activated astrocytes in the dorsal parts of the striatum bilaterally. One may conclude that a parkinsonian model induced by rotenone is characterized by degenerative changes of dopamine neurons in the s. nigra, with α-synuclein aggregation and local and symmetrical injury of the striatum (with the involvement of dopaminergic fibers, neurons, neuroglia and cerebral vessels), which presumably reflects rotenone-induced mitochondrial dysfunction.

 
Annals of Clinical and Experimental Neurology. 2013;7(2):34-38
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Reviews

Genetics of hereditary forms of dystonia

Krasnov M.Y., Timerbaeva S.L., Illarioshkin S.N.

Abstract

Dystonia is one of the most common movement disorders with great medical, social and economic importance. Genetics plays significant role in the development of different, and mainly primary, forms of dystonia. At present the range of hereditary dystonic syndromes comprises more than twenty separate clinicalgenetic variants, which characterizes dystonia as a highly heterogeneous nosologic group calling for differentiated approaches to diagnosis and treatment. Detailed analysis of the literature on hereditary forms of dystonia, including clinical picture, molecular genetic basis, phenotype–genotype correlations, and principles of DNA diagnostics and medical genetic counseling of affected families, is presented.

 
Annals of Clinical and Experimental Neurology. 2013;7(2):55-62
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Technologies

Current means for identifying the latent stage of a neurodegenerative process

Illarioshkin S.N., Vlassenko A.G., Fedotova E.Y.

Abstract

A characteristic feature of neurodegenerative diseases is the presence of a long-term latent stage, while manifestation of symptoms occurs after 40–60% cells loss in vulnerable neuron populations. Therefore, potential for neuroprotection is maximal just at the latent stage of the process. In this paper, current technologies of presymptomatic diagnosis of the two most common neurodegenerative disorders, Alzheimer’s and Parkinson’s
disease, are presented. On the basis of our own experience and data from the literature it is shown that neuroimaging methods (identification of beta-amyloid in the brain, or phenomenon of hyperechogenecity of the s.nigra, etc) in combination with a number of neurophysiological and molecular/pathobiochemical tests are principal in revealing persons with high risk of these disorders. Validation of biomarkers under discussion and their integration
into uniform diagnostic screening algorithms is at present one of the most actual fields of neurology.

Annals of Clinical and Experimental Neurology. 2013;7(2):39-50
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Clinical analysis

A new allelic variant of rigid spine syndrome

Dadali E.L., Kadnikova V.A., Sharkova I.V., Polyakov A.V.

Abstract

Description of clinical features of the disease in a 4-year-old boy with rigid spine syndrome is presented. Molecular genetic analysis revealed in this patient an unknown homozygous mutation 988delC in the SEPN1 gene (coding for selenoprotein N). In contrast to previously described selenoprotein-associated cases of the disease, our patient exhibited early involvement in the pathological process of muscles of the shoulder and the pelvic girdles.

 
Annals of Clinical and Experimental Neurology. 2013;7(2):51-54
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