[Botulinum toxin type A (Relatox) in transition from medication overuse to non-overuse status in patients with chronic migraine: a subgroup analysis of phase IIIb randomized single-blind multicenter active-controlled parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v preodolenii lekarstvennogo zloupotrebleniya u patsientov s khronicheskoi migren'yu: podgruppovoi analiz rezul'tatov mnogotsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO). MATERIAL AND METHODS: In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures. RESULTS: Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050). CONCLUSION: The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

[Botulinum toxin type A (Relatox) in the treatment of chronic migraine in adults: results of phase IIIb, randomized, one-blind, multicenter, active-controlled, parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v lechenii khronicheskoi migreni u vzroslykh: rezul'taty mul'titsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM). MATERIAL AND METHODS: The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score. RESULTS: Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified. CONCLUSION: The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

[Migraine burden and clinical inertia: what can we do?] / Migren' i klinicheskaia inertsiia: chto my mozhem sdelat'?

AIM: To study the compliance of neurologists and headache specialists to chronic headache and chronic migraine (CM) diagnosis and treatment guidelines. MATERIAL AND METHODS: The survey included 634 neurologists from all regions of the Russian Federation. Mean age of respondents was 40.7±8.5 years, mean years of experience 14.2±7.8 years. RESULTS: Most doctors work in outpatient or hospital settings (49% and 24%, respectively), 7% were headache specialists. Tension-type headache (TTH) was diagnosed in 30% and CM in 17% of patients while 44% of patients were presumed to have a mixed headache disorder (TTH+CM). Only 10% of physicians do not use instrumental diagnostic methods in chronic headache. This study has shown sufficient attention to comorbid conditions and frequent prescription of headache preventative treatment. Botox prescription data is equivocal: 35% of physicians recommend such treatment, 27% do not, while other doctors prescribe it for off-label indications. CONCLUSION: To overcome clinical inertia, further education in chronic headaches and their optimal treatment is warranted.

[Experience of using the chondroprotector Sustagard Artro (sashe) in the treatment of lower back pain]. / Opyt primeneniia khondroprotektora Sustagard Artro (poroshok) pri boliakh v nizhnei chasti spiny.

AIM: To compare the efficacy of oral administration of the chondroprotector (CP) Sustagard Artro and nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing lower back pain and to assess the level of blood glucose in patients taking CP. MATERIAL AND METHODS: Sixty patients with spondylarthrosis (SA) were studied. Patients were randomized into the CP group (n=30), which received Sustagard Artro (1 sachet once a day for 6 weeks), and the NSAIDs group (n=30) treated with injectable forms of different groups of NSAIDs for 3-7 days. Pain intensity was evaluated by the numerical rating scale (NRS) and the Oswestry disability index (ODI). RESULTS: The reduction in the severity of pain on NRS was similar in both groups: 5.73±1.74 before treatment and 1.43±0.33 after treatment in the CP group; 6.03±0.93 and 1.17±0.97 in the NSAIDs group, respectively. No significant difference in the efficacy was observed between two groups on ODI: 34.66% at baseline and 1.86% after 6 weeks in the CP group; 37.47% and 2.27% in the NSAIDs group, respectively. Changes in the level of glucose were within the upper limit of normal in the CP group. CONCLUSION: Oral administration of CP (Sustagard Artro, sashe) reduces pain syndrome as effectively as NSAIDs.

[Real-world migraine burden: clinical and economic aspects]. / Bremia migreni v real'noi klinicheskoi praktike: klinicheskie i ékonomicheskie aspekty.

AIM: To evaluate the rationale for different approaches to preventive chronic migraine (CM) treatment by comparing clinical outcomes and financial burden of the disease in the real-world practice. MATERIAL AND METHODS: Sixty-six patients with CM were enrolled at the Alexander Vein Headache Clinic (60 women and 6 men, aged 28-51). All patients were divided into 3 groups: group 1 (n=22) received oral preventative treatment with topiramate, up to 100 mg daily, for three months; group 2 (n=20) received 12 acupuncture sessions (3 sessions a week); group 3 (n=24) received 155-195 units of botulinum toxin type A (botox, BTA). The follow-up period in all groups was 3 months. Efficacy was evaluated by clinical examination, the Headache Impact Test (HIT-6) and questionnaires to assess subjective patient satisfaction and treatment tolerability. RESULTS: BTA demonstrated the highest efficacy in this study. Compared to the oral preventative treatment and acupuncture, BTA reduced the frequency of headache faster and more significantly facilitating CM transformation into episodic migraine (headache frequency was 16.1±0.1; 18.0±0.02; and 13.9±0.3 in groups 1, 2 and 3, respectively, after one month of treatment). BTA also improved the quality of life faster and more significantly and was better tolerated (good - 51%, 75% and 85% in groups 1, 2 and 3, respectively; satisfactory - 35%, 25% and 15% in groups 1, 2 and 3, respectively; bad 14% in the oral prevention group). In the BTA group, the majority of patients demonstrated earlier treatment satisfaction. Despite higher (compared to topiramate) direct costs in the BTA group (RUB 29 931.51 and RUB 32 085.87, respectively), the predicted cost of a headache-free day was the smallest and totaled RUB 652.15 (compared to RUB 692.86 and RUB 1017.60 in the topiramate and acupuncture groups, respectively). CONCLUSION: The data on the efficacy and costs of different CM prevention strategies would facilitate optimal treatment choice for neurologists and patients.

[Diagnosis and treatment of migraine: Recommendations of the Russian experts]. / Diagnostika i lechenie migreni: rekomendatsii rossiiskikh ékspertov.

These recommendations on the diagnosis and treatment of migraine were elaborated by Russian headache experts in accordance with the evidence-based practice. Together with the latest classification, diagnostic principles and criteria of different clinical sub-forms the consensus contains basic data on migraine epidemiology, pathophysiological mechanisms, differential diagnosis and most effective and evidence based approaches to pharmacological and non-pharmacological management of migraine patients.

[Diagnosis of refractory forms of chronic primary headache]. / Diagnostika refrakternykh form khronicheskoi pervichnoi golovnoi boli.

A number of patients with primary headaches remain insensitive or refractory to treatment despite correctly selected drugs, adequate therapeutic dose and duration of therapy. The importance of refractory problem is determined by the fact that patients are completely maladjusted, disabled, and keeping these patients is very difficult even for seasoned professionals. Determination of the correct tactics and success of the treatment depends, in the first place, on the correct diagnosis. This article discusses the diagnostic criteria for the most important forms such as refractory chronic migraine or refractory chronic cluster headache presented by experts of the European Headache Federation in two separate Consensus.

[Selection of a dose of the botulinum toxin A in spastic forms of cerebral palsy]. / Vybor dozy preparata botulinicheskogo toksina tipa A pri lechenii spasticheskikh form detskogo tserebral'nogo paralicha.

AIM: To analyze the efficacy and safety of dose ranges of abobotulinum toxin A (BTA) for multilevel injections into upper and lower extremity muscles in children with spastic forms of cerebral palsy (CP). MATERIAL AND METHODS: We analyzed retrospectively multilevel BTA injections for 216 patients, aged from 2 to 17 years. Children received 1-6 repeated injections and complex physiotherapy. Patients were classified according to the GMFCS. Treatment results were evaluated with the modified Ashworth and Tardieu scales. RESULTS: Multilevel BTA injections were indicated for the most (89/8%) of the patients with spastic forms of CP, and in most of them the total dosage exceeded 30 U/kg. In the bilateral forms of CP, the total dosage (U and U/kg) was higher compared to the unilateral forms. Doses for each muscle in U/kg were similar in all CP forms. The total doses of BTA and the intervals between the repeated injections were stable for each patient. CONCLUSION: The dose ranges suggested for CP are effective and safe for the reduction of spasticity in several functional segments of upper and lower extremities in one treatment session.

[Principles of interviewing in the diagnosis of chronic migraine].

Chronic migraine (CM) is the most prevalent disabling primary daily headache disorder, the prevalence of CM in Russia is 3 times as much as worldwide (6,8% vs 2% respectively). The diagnosis of CM is based on the International Classification of Headache Disorders 3rd edition (beta-version) dated 2013. (ICHD-III). Not all the physicians are fully aware and/or actively use the diagnostic criteria stated in the ICHD-III. Underdiagnosis of CM causes the inadequate treatment that is still the problem for both GPs and neurologists. This article reviews in detail the specific principles of clinical interview that is critically important to evaluate the status of the patient. The use of special clinical scales, questionnaires, diaries helps to diagnose CM and other co-morbid mental and somatic disorders, to evaluate disability and decreased migraine related quality of life. The interpretation of the findings remains the most important point to diagnose CM, to define the need of additional exams and to evaluate the efficacy of therapy.

[An electromyographic study on the development of optimal tactics of botulinum toxin type A injections in children with spastic forms of cerebral palsy].

We studied 67 children, aged 2-9 years, with cerebral palsy including 56 children with a spastic form. An electromyographic method was used for the development of optimal tactics of botulinum toxin type A injections in different clinical presentations of spasticity. The best clinical results were obtained in children with the following changes on EMG: 1) the tonic muscle activity in resting state was minimal (<10 microvolts) and had local or regional distribution; 2) the pathological synkinetic activity during voluntary movements was minimal (synergetic activity coefficient for shin muscles was less than 0.45); 3) the disturbance of interactions between synergistic and antagonistic muscles was moderate (reciprocity coefficient was not less than 0.4); 4) EMG amplitude in voluntary muscle contraction should not be less than 150 microvolts. This approach to the treatment allowed to reach higher levels on The Gross Motor Function Classification System in part of children.

[Foot deformity in children with spastic forms of cerebral palsy: the treatment with botulinum toxin type A (dysport)].

The objective is to study the effect of dysport injections on the clinical and electromyographic changes in 35 patients (mean age 5,3+/-2,0 years) with spastic forms of cerebral palsy (26 with spastic diplegia, 9 with hemiparetic form) with equinus and equinovarus deformity. Depending on the clinical situation, dysport was injected in a total dose of 20-30 u per 1 kg of the body mass. Gastrocnemius muscles were injected more frequently than soleus and posterior tibial muscles. The treatment resulted in the significant reduction of spasticity on the Ashworth scale, decrease of equinus deformity, positive changes in the parameters of stepping on flat foot, independent standing and walking, the beginning of support period from the heel. During the arbitrary contraction, the amplitude of bioelectrical activity of target muscles of low extremities reduced, though not to the extent of the motor activity loss; the reciprocity coefficient decreased from 0,69+/-0,32 to 0,47+/-0,28 in patients with spastic diplegia and from 0,45+/-0,34 to 0,34+/-0,25 in patients with hemiparetic form. The effect of dysport was higher in hemiparetic form compared to spastic diplegia. The best results for spastic diplegia were revealed in patients with isolated spasticity without severe disturbances of reciprocal relations in shin muscles and pathological synkinesia.

[Duloxetine in the treatment of chronic migraine].

The aim of the study was to investigate the influence of duloxetine on clinical parameters and antinociceptive mechanisms in 46 patients with chronic migraine (CM). In addition to a clinical examination, we performed a neurophysiological investigation which included blink reflex (BR) and nociceptive flexion reflex (NFR) tests. From the beginning of the treatment with duloxetine (60 mg/d) to the third month of treatment, the number of days with headache decreased from 25,8+/-5,3 to 10,5+/-3,9 (p< or =0,001); the frequency of migraine attacks/month decreased from 11,3+/-3,8 to 6,8+/-2,5 (p< or =0,001); the amount of analgesic tablets used per month decreased from 46,6+/-14,7 to 8,5+/-10,6 (p< or =0,001). The reduction of the number of days with headache by more than 50% and more than 30% was noted in 50% and 57,5% of patients, respectively. The treatment with duloxetine resulted in the significant increase of the pain and NFR thresholds as well as in the normalization of the RIII threshold and its habituation in BR. These results confirmed the role of duloxetine in increasing of the noradrenergic and serotonergic activity of brain antinociceptive systems in patients with CM. The clinical effectiveness of duloxetine can be explained by its multilevel modulatory influence on the pathogenetic mechanisms of CM including the activity of antinociceptive systems of the brainstem and of brain nociceptive systems through the decrease of central sensitization.

Effects of topiramate on migraine frequency and cortical excitability in patients with frequent migraine.

We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 +/- 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 +/- 1.3 to 5.8 +/- 3.2 migraine days per month; P = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 +/- 7.5% to 47.7 +/- 9.2% (P = 0.049) and on the left side from 43.4 +/- 7.0% to 47.2 +/- 9.6% (P = 0.047), and phosphene thresholds increased from 58.9 +/- 11.1% to 71.2 +/- 11.2% (P = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.

[Efficacy of duloxetine in the treatment of chronic daily headache].

An aim of the study was to assess effect of duloxetine, a selective inhibitor of serotonin and noradrenalin reuptake, on chronic daily headache (CDH) and its antinociceptive mechanisms. Duloxetine was administered in dosage 60 mg per day during 8 weeks to 40 patients. The high efficacy of the drug by different clinical indices--decrease of days of headache per month, frequency of headache attacks, reduction of analgetics used--was found, all changes being statistically significant. The therapeutic response was developed from the 2nd month of the treatment. The study of the nociceptive flexion reflex revealed the increase of its threshold and of subjective pain threshold as well. Intensity of comorbid disorders, depression and anxiety, was also significantly decreased. Side-effects were small and transient.

[The phototherapy of parkinsonism patients]. / Fototerapiia bol'nykh parkinsonizmom.

40 patients with idiopathic parkinsonism were treated by artificial white light (intensity--3300 lux) together with total or partial "drugs holidays". The patients with newly made diagnosis "parkinsonism" were treated too. Both before and after light therapy (LT) (10 light exposures) we performed estimation of the main clinical manifestations of the disease (in rating scales), psychological assessment (Back's depression rating scale), examination of motility (authors' own special computer program "Hand's Movement Test for Windows"). It was observed that LT resulted in a decrease of the severity of either rigidity or bradykinesia (but not the tremor) as well as it also decreased the depression gravity and improved the motor functions. LT facilitated the patients' capacity to tolerate "the drugs holidays". LT permitted to combine it with drug therapy as well as LT decreased the complications of DOPA-containing drugs (on-off-effects and dystonic hyperkinesias). LT may be used as monotherapy in patients with initial manifestations of the disease. LT didn't cause any complications and was quite simple in carrying out. The conclusion is made about the perspectivity of LT application in parkinsonism treatment as important non-drug therapy.