Use of the new levodopa agent Stalevo (levodopa/carbidopa/entacapone) in the treatment of Parkinson's disease in out-patient clinical practice (the START-M open trial).

Despite the significant symptomatic effects of levodopa, stable 24-h treatment responses are in the vast majority of patients replaced 2-3 years from the start of treatment by oscillations in motor symptoms (fluctuation, dyskinesia), amelioration of which requires addition of constant (physiological) stimulation of postsynaptic dopamine receptors. To some extent this is provided by Stalevo, which contains levodopa and two enzyme inhibitors: the DDC inhibitor carbidopa and the COMT inhibitor entacapone. The results obtained in the present study demonstrated the advantages of Stalevo over traditional agents in patients with the "wearing off" and "on-off" phenomena.

[Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. / Asteniia, émotsional'nye rasstroistva i kachestvo zhizni u patsientov s rasseiannym sklerozom.

Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome, emotional disorders and quality of life of patients with multiple sclerosis (MS) and to explore the possibility of using idebenon (noben) in treatment of these impairments. Material and methods. We studied 35 patients, 18 men and 17 women, with MS (mean age 36.4±8.86 years, mean disease duration 10.33±6.07 years); 83% of patients had remitting type and others - secondary progressive type. Along with neurological examination, we used the Modified Fatigue Impact Scale (MFIS 21), the Hospital Anxiety and Depression Scale and a quality of life questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at baseline. The old age of the patients and duration of MS and its severity according to EDSS predicted the higher levels of asthenia, chronic fatigue and anxiety with depression and lower quality of life on EQ5D. All patients received noben in dosage 90 mg daily (30 mg 3 times a day) during 6 months. Results and conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome, asthenia and depression in MS patients. The dose used in the study may be regarded as the optimal dose that provides best efficacy with minimal side-effects.

[Emotional disorders and quality of life in patients with post stroke asthenia].

An aim of the study was to assess the severity of asthenic syndrome, emotional disorders and quality of life indicators in post stroke patients treated with idebenone (noben). We studied 35 patients aged from 47 to 76 years, mean age 58,85±7,99 years, 21 men and 14 women. The time after stroke was 1-8 years (mean 2,63±1,51 years). The duration of follow-up was 6 months. Patients were examined at baseline and 3 and 6 months after treatment with noben in dose 90 mg daily (30 mg 3 times a day). Patients were examined clinically, the following scales were used as well: the Scandinavian stroke scale, the modified MFIS-21, the hospital anxiety and depression scale (HADS) and EQ5D including VAS. It has been shown that asthenic syndrome negatively influenced quality of life and emotional sphere thus impeding the recovery of daily activities. The follow-up study revealed that the treatment with idebenone in dose 90 mg daily decreased the severity of asthenia and emotional disorders and significantly improved quality of life.

[Possibilities of medical correction of moderate cognitive impairment].

Thirty-four outpatients with moderate cognitive impairment were treated with one of standard extracts of Ginkgo Biloba - EGb761 (memoplant). Memoplant was used in high dosages (240 mg daily) twice a day during three months. Patients were assessed using the Montreal Cognitive Assessment (MoCA), the hospital depression scale and QoL questionnaire EQ5d as well as standard neurological and somatic examination. A statistical analysis of data revealed a significant improvement in most measures, mostly in attention, memory, orientation and visual-spatial/ executive functions as well as in anxiety and depression. The drug is well-tolerated and is recommended for practical use.

[Experience in using xeomin in the treatment of arm and hand spasticity in the early rehabilitation phase of stroke].

To reduce arm and hand spasticity, 28 patients in the early rehabilitation phase of ischemic hemisphere stroke received injections of the botulinum toxin A preparation xeomin in the content of complex rehabilitation programs. The following muscles: m. biceps brachii, m. flexor digitorum profundus, m. flexor digitorum superficialis, m. flexor carpi ulnaris, m. flexor carpi radialis were injected according to standard scheme. The total dose of drug was 200U in moderate (2-3 scores on the Ashworth scale) and 300U in marked (3-4 scores on the Ashworth scale) spasticity. Efficacy and safety of treatment was assessed at baseline and 2, 4, 8, 12, 16 weeks after injections. Xeomin significantly (p<0.05) reduced muscle tonus in patients with post-stroke spasticity of different severity. Clinical effect was seen 2 weeks after injection, it reached maximum at week 4 and then slowly decreased to week 16. The improved functional activity of the paretic arm (due to patient's and caregiver's reports) remained for to 12 weeks. The treatment was most effective in the group of patients with moderate spasticity. The correlation analysis confirmed that the severity of spasticity increased with the disease duration that reduced rehabilitation efficiency. The treatment with xeomin was safe, no serious side-effects were found.

[The role of dopamine in the regulation of the interaction between nervous and immune systems in multiple sclerosis].

A complex neurological and neuropsychological examination, including the detection of depression, was conducted in 71 patients with multiple sclerosis aged from 23 to 62 years (mean age 43 ± 9 years). An immunobiochemical study included the analysis of expression of CD80 and CD86 on monocytes and B-cells, expression of TLR2 and TLR4 on monocytes, expression of D3 and D5 dopamine receptors on monocytes and B-cells, using flow cytometry, and the determination of Il-6, Il-10, IL-12p40 and dopamine plasma levels as well as vanillylmandelic acid (VMA, dopamine metabolite) urine levels measured with immunoenzyme assay. The results suggest the involvement of dopamine in the pathogenesis of depression in MS as assessed by dopamine and its metabolites levels. The role of dopamine and monocyte activation (by TLR2) in the pathogenesis of cognitive disturbances was specified as well.

[Treatment of vestibular vertigo and Ménière syndrome in outpatient clinics].

An aim of this study was to assess clinical efficacy and tolerability of tagista in the symptomatic treatment of vestibular vertigo and Ménière syndrome. Thirty-two patients, 16 women and 16 men, aged from 25 to 67 years, were examined. Vertigo was caused by chronic brain ischemia in 17 cases and by the disturbance of blood circulation in the vertebral-basilar system in 14 patients with osteochondrosis of cervical spine. One patient was diagnosed with Ménière syndrome. Tagista was used in dose 24 mg twice a day during 4 weeks in the combination with standard treatment, exercise therapy and stability training. The results revealed a statistically significant effect of the drug on main symptoms (frequency, duration and intensity of vertigo attacks etc) and its good tolerability that allowed to recommend the drug in neurological practice.

[The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease].

The main aim of the study was the evaluation of the efficacy and drug safety of cerepro (choline alfoscerate) used for treating outpatients with cerebrovascular disease. Ninety patients with cerebrovascular disease, who had motor, coordination, emotional and cognitive disturbances were enrolled in the study. Sixty patients of the group 1 had stroke, 30 patients (group 2) had chronic ischemic brain disease. All patients received basic therapy (antihypertensive, antiaggregant or anticoagulant, cholesterol-lowering drugs). Cerepro was administrated in combined therapy according to the scheme: 1000 mg cerepro (in 200 ml of the 0.9% NaCl solution) once a day intravenously in drops during 10 days; then 1200 mg daily per os during 6 weeks. We assessed the dynamic of neurological symptoms and restoration of lost functions (MMSE, Feeling-activity-mood test, HDRS, GCI). The results indicate the efficacy of cerepro in outpatients with chronic cerebrovascular disease and stroke. It was demonstrated that cerepro led to improvement of coordination neurological symptoms, cognitive and emotional functions, activity and mood in patients of both groups. Clinical effect was higher in patients after stroke. Cerepro was well tolerated.

[Effect of dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease].

The open 6-month study (the MIRAG study) on the effect of D2/D3 dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease (PD) was carried out. Ninety-eight patients, aged from 42 to 75 years (mean age 63.2+/-10.2 years) were included in the study. Scores on the Hoehn and Yahr scale varied from 1 to 4 (mean 2,5+/-0,8). Seventy percent of patients received levodopa in average dose 351.2+/-279.4 mg; 62% of patients had motor fluctuations and 43% had dyskinesias. Pramipexole was titrated to the effective dose (maximum 3 mg/d, mean 2.1 mg/d). In the end of the study, resting tremor was reduced by 54%, postural and kinetic tremor, as assessed with UPDRS and spirography, by 50% and 15%, respectively. The severity of depressive symptoms measured with the Montgomery-Asberg Scale and a modified version of the Geriatric-Depression Scale (GDS-15) was reduced by 56%. Motor fluctuations and dyskinesias were significantly reduced while cognitive functions were not changed. The clinically significant effect reflected in the reduction of motor and non-motor symptoms was observed in 83% of patients, regardless of disease duration, severity of motor deficit, affective and cognitive disorders,. The drug was well tolerated in all patients, including those older than 70 years. Pramipexole improved quality of life in PD patients due to the attenuation of cardinal motor parkinsonian symptoms as well as symptoms, which were relatively resistant to levadopa, e.g. postural and kinetic tremor, and depression. The therapeutic effect remained for at least 6 months.

[Influence of dopamine agonist pramipexole (mirapex) on tremor, cognitive and affective impairment in patients with Parkinson's disease].

The open 3-month study of influence of D2/D3 dopamine agonist pramipexole on of Parkinson's disease (PD) features, which are relatively resistant to traditional dopaminergic therapy: tremor, affective and cognitive impairment, has been conducted. Ninety-eight patients with PD, aged from 42 to 75 years (mean age 63,2+/-10,2 years), have been included in the study. Twenty percents of patients included were older than 70 years. The Hoehn and Yahr stage varied from 1 to 4 (men stage 2,5+/-0,8). Seventy percents of patients received levodopa (mean dosage 351,2+/-279,4 mg); 62% had motor fluctuations and 43% - dyskinesias. Pramipexole was titrated to effective dose (maximum 3 mg/d, mean 2,1 mg/d). The decrease of resting tremor by 50% and postural and kinetic tremor (assessed with the UPDRS and spiralography) by 37% was noticed to the end of 3 month. The severity of depressive symptoms measured with the Montgomery-Asberg scale and a modified version of the Geriatric Depression scale was reduced by one third. The statistically significant decrease of motor fluctuations and dyskinesias, increase of verbal fluency (but not other cognitive functions) were also found. The clinically significant effect of reducing of motor and non-motor symptoms was seen in 86% patients regardless of their age, illness duration, severity of motor deficit and affective and cognitive disturbances. The fair tolerability of the drug was shown including patients older than 70 years.

[The study on the assessment of the new levodopa drug--stalevo (levodopa/carbidopa/entacapone), in treatment of Parkinson's disease in out-patient clinical practice (the results of the open START-M)].

Despite significant symptomatic effect of levodopa, in most patients the stable 24 hour's effect changed for alterations of movement symptoms (fluctuations, dyskinesia) after 2-3 years of the therapy. These complications may be reduced due to the constant (physiologic) stimulation of post-synaptic dopamine receptors that, to a certain degree, provides the drug stalevo, which contains levodopa and 2 enzyme inhibitors, dopa decarboxylase (carbidopa) and catechol-O-methyltransferase (entacapone). The results of the study demonstrated beneficial effects of stalevo as compared to traditional therapy in patients with "wearing off" and "on-off" phenomena.

[The use of the drug ginos in the treatment of out-patients with chronic progressive brain disorders].

Ginos, a derivative of extract Ginkgo Biloba, was administered to 100 patients, aged from 45 to 80 years, mean age 62,3+/-0,7), in dosage 120 mg 3 times daily during 3 months in addition to somatic therapy. A patient's state was assessed before, during and after the treatment using clinical methods and a battery of psychometric scales and neuropsychological tests. A significant improvement of neurological and mental status was found in 90 (90%) of patients that was most distinctly observed in the dynamics of their global state and neurocognitive performance on the MMSE and other tests. The effect of the drug was less pronounced for affective disorders - depression and anxiety. The drug was well-tolerated by patients.

[Use of tremonorm in treatment of Parkinson's disease: outpatient experience of Moscow Municipal Health Care Service]. / Primenenie tremonorma pri bolezni Parkinsona: opyt ambulatornoi nevrologicheskoi sluzhby Moskovskogo gorodskogo zdravookhraneniia.

The efficacy of domestic drug tremonorm (levadopa-carbidopa) for Parkinson's disease (PD) treatment was studied. The treatment was conducted in neurological outpatient departments in several Moscow administrative regions and was administered to 142 PD patients, 15 being assigned to this drug for the first time and 127 being previously treated with other medications containing levadopa/carbidopa. A minimal effective dose (up to 500 mg) was selected for each patient and was not changed during 2 months. For patients previously switched to levadopa, the change for tremonorm has been done during 1 day if the dose of levadopa did not exceed 500 mg, and during 2 months in case a patient received over 500 mg per day. Modified Hoehn&Yahr scale, UPDRS, MMSE, PDQ-39 and other scales were used in complex evaluation of the disease stage. Positive effect of tremonorm was detected for 94 patients (66.2%), all of them continued tremonorm therapy after the end of the study. The most frequent side-effects proved to be dyspeptic symptoms. Tremonorm caused statistically significant positive changes in patient's movement scaled by UPDRS and the QL indexes in all PDQ-39 subscales. Positive changes in movement activity were accompanied by decrease of bradykinesia, tremor, better walking, writing and every day activity of PD patients. A change of nacom for tremonorm did not result in significant alteration of symptoms and Quality of Life indexes that suggest similar influence of these drugs on PD symptomatology. At the same time, a substantially lower price of tremonorm allows reducing of treatment costs.