[Issues of diagnostic and therapeutic use of transcranial magnetic stimulation in patients with writing cramp]. / Voprosy diagnosticheskogo i terapevticheskogo primeneniya transkranial'noi magnitnoi stimulyatsii u patsientov s pischim spazmom.

OBJECTIVE: To study diagnostic and therapeutic values of transcranial magnetic stimulation (TMS) in writing cramp (WC). MATERIAL AND METHODS: Twelve right-handed patients with WC were enrolled in the study. All patients underwent low-frequency repetitive TMS (rTMS) of the premotor cortex of contralateral to affected hand hemisphere. The clinical efficacy was assessed using the Writer's Cramp Rating Scale (WCRS) and the Medical Outcomes Study-Short Form (MOS-SF-36). Before and after last rTMS session, motor mapping of Abductor pollicis brevis muscle (APB) was performed using navigated TMS (nTMS). Localization, area, and amplitude-weighted area of the APB muscle cortical representations were compared with the healthy controls. After the rTMS course, the dynamics of the studied parameters was assessed. RESULTS: Ten sessions of low-frequency rTMS of premotor cortex reduced the severity of WS clinical symptoms with a duration of effect of at least 1 month (p<0.05). There was no statistically significant difference between the area and the weighted area of cortical muscle representations between patients and healthy controls or in patients before and after rTMS. When assessing the localization of cortical muscle representations, two trends were noted: in 4 patients, the localization remained stable, with a shift in the center of gravity of less than 4 mm; in the other 8 patients, a shift in the center of mass of more than 5 mm was noted. No significant correlation between the stability of the cortical muscle representations (the magnitude of the shift in the center of gravity) and the improvement on the WCRS were found. CONCLUSION: The low-frequency rTMS of the premotor cortex of the contralateral to affected hand hemisphere can be used as an adjuvant therapy for WC. The TMS-motor mapping study did not show its diagnostic value.

[Diagnostic and therapeutic issues of using transcranial magnetic stimulation in patients with writer's cramp]. / Voprosy diagnosticheskogo i terapevticheskogo primeneniia transkranial'noi magnitnoi stimuliatsii u patsientov s pischim spazmom.

AIM: To assess diagnostic and therapeutic values of transcranial magnetic stimulation (TMS) in patients with writer's cramp (WC). MATERIAL AND METHODS: Twelve right-handed patients with WC were enrolled in the study. All patients underwent low-frequency repetitive TMS (rTMS) over the premotor cortex of the hemisphere contralateral to the affected hand. The clinical efficacy was assessed using the Writer's Cramp Rating Scale (WCRS) and the Medical Outcomes Study-Short Form (MOS-SF-36). Before and after the last rTMS session, motor mapping of abductor pollicis brevis muscle (APB) was performed using navigated TMS (nTMS). Localization, area, and amplitude-weighted area of the APB muscle cortical representations were compared with the healthy controls. The dynamics of the mentioned above parameters after the rTMS course was assessed. RESULTS: Ten sessions of low-frequency rTMS over premotor cortex reduced the severity of WC clinical symptoms, with a duration of effect of at least 1 month (p<0.05). There was no significant difference between the area and the weighted area of cortical muscle representations between patients and healthy controls or in patients before and after rTMS. When assessing the localization of cortical muscle representations, two trends were noted: in 4 patients, the localization remained stable, with a shift in the center of gravity of less than 4 mm; in the other 8 patients, a shift in the center of gravity of more than 5 mm was noted. No significant correlations between the stability of the cortical muscle representations (the magnitude of the shift in the center of gravity) and the improvement on the WCRS scale were found. CONCLUSION: The low-frequency rTMS over the premotor cortex of the hemisphere contralateral to the affected hand can be used as an adjuvant therapy for WC. The TMS-motor mapping study did not show its diagnostic value.

[Unilateral posteroventral pallidotomy in the treatment of drug-induced dyskinesia in Parkinson's disease]. / Odnostoronniaia posteroventral'naia pallidotomiia v lechenii lekarstvennykh diskinezii pri bolezni Parkinsona.

OBJECTIVE: to determine the efficacy of unilateral posteroventral pallidotomy (PVP) in the treatment of drug-induced dyskinesia (DID) in Parkinson's disease (PD). MATERIAL AND METHODS: We analyzed surgical treatment of 14 patients with PD complicated by DID who underwent unilateral PVP at the Research Center of Neurology in the period between 2012 and 2015. The clinical type of DID was mainly represented by peak-dose choreoathetoid dyskinesia, more pronounced in the distal limbs, and predominantly unilateral. The severity of drug-induced dyskinesia was assessed on the UPDRS scale (part IV-A) before surgery and at 1 week and 6 months after surgery. RESULTS: One week after pallidotomy, all of the 14 patients had a regression of contralateral dyskinesia by 68.3±9.7%; 50% of patients had a regression of ipsilateral dyskinesias by 43%, on average. In 50% of cases, the dose of levodopa was reduced by 15%, on average. On examination at 6 months after surgery, regression of contralateral dyskinesia was 55.7±8.8%, and the severity of ipsilateral DID returned to the preoperative level. The use of pallidotomy significantly improved the indicators of daily activity and quality of life of patients. There were no significant postoperative complications. Three patients had mild speech disorders in the form of dysarthria, which regressed 2-3 weeks after surgery.

[Conversion ratio between different botulinum neuroprotein product in neurological practice]. / Sootnoshenie edinits deistviia razlichnykh preparatov botulinicheskogo neiroproteina pri ispol'zovanii v nevrologicheskoi praktike.

Despite nearly 30 years of experience in the application of botulinum toxin type A (BTA) in clinical practice, many fundamental questions of therapy remain valid. There are 5 botulinum toxin type A used for neurological indications in the Russian Federation in 2017. They contain different number of active neuroprotein (150 kDa) in a therapeutic dose of the drug that may have a potential impact on the efficacy and duration of action. The current SmPC of each BTA stated that the unit of activity is unique and can not be compared with any other BTA. In scientific publications one can find many details concerning the equivalence doses of onabotulinumtoxin A (botox) and abobotulinumtoxin A (dysport) and the ratio of units varies from 1:1 to 1:11. However, according to clinical guidelines, systematic reviews and high quality research evidence of recent years, the ratio of units of abobotulinumtoxin A (dysport) and onabotulinumtoxin A (botox) is 3(2,5):1. Use of a fixed ratio of units is possible only when switching from one drug to another or in case of limiting access to specific drug. Botulinum toxin type A is the first line of therapy in the treatment of several neurological diseases. The most commonly used drugs of botulinum toxin type A (botox, dysport, xeomin) have a significant evidence base that confirms their efficacy and optimal safety profile. The main difference between botulinum toxin type A is their potential activity of action, i.e., activity units and total therapeutic dose.

[Differential diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy]. / Differentsial'naia diagnostika tserebral'noi autosomno-dominantnoi arteriopatii s podkorkovymi infarktami i leikoéntsefalopatiei.

Cerebral autosomal dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) is an inherited CNS disease, which is caused by mutations in the NOTCH3 gene. Selective disorders of small vessels underlie the disease pathogenesis. Clinically CADASIL is characterized by headaches, multiple stroke-like disorders (in most cases transient ischemic attacks and lacunar strokes), and different focal neurological symptoms and dementia. There are specific MRI signs of the disease: multiple lacunar infarctions located in the basal ganglia, brain steam and cerebellum, focal lesions of temporal poles, capsula externa, periventricular and subcortical areas; diffuse white matter changes and leukoaraiosis can be observed as well. The differential diagnosis of CADASIL is made with many diseases, which are manifested by multiple brain matter lesions, including demyelinating disorders. It should be taken into account that CADASIL is characterized by headaches as one of the initial symptoms, multiple lacunar and diffuse brain matter lesions based on MRI data with an absence of atherosclerosis and arterial hypertension. Family history and autosomal dominant mode of inheritance is also typical of CADASIL. Detection of the NOTCH3 gene mutation is necessary for the definite diagnosis of CADASIL.

[The effect of antioxidants on in vivo and in vitro methemoglobin formation in erytrocytes of patients with Parkinson`s disease].

Methemoglobin formation was examined in erytrocytes of 16 patients with Parkinson`s disease (PD) (stage 3-4 by the Hoehn and Yahr scale). The patients receiving levodopa-containing drugs (madopar, nakom) were also treated with intramuscular injections of mexidol (daily dose 100 mg/day) for 14 days. Control group included 12 clinically healthy persons. The erythrocyte methemoglobin content was determined by electronic paramagnetic resonance (EPR) using the EPR signal intensity with g-factor 6.0. The methemoglobin content was significantly higher in erythrocytes of PD patients than in healthy donors. The complex therapy with mexidol normalized the methemoglobin content in erythrocytes of PD patients. Incubation in vitro of erythrocytes of donors and PD patients with acrolein increased the methemoglobin content, while incubation with carnosine normalized the methemoglobin content in erythrocytes of PD patients. Prophylactic (i.e. before acrolein addition) and therapeutic administration of carnosine to the incubation system with acrolein decreased the methemoglobin content to its initial level. Results of this study suggest that inclusion of the antioxidants mexidol and carnosine in the scheme of basic therapy of PD may reduce side effects associated with methemoglobinemia.

[An analysis of treatment of the Russian group of patients in the international observational study «Factors influencing response to botulinum toxin type A in patients with idiopathic cervical dystonia¼].

AIM: The analysis of the results of treatment of the Russian patient population in the frame of international, multicenter, non-interventional study of CD, the primary purpose of which was to determine the response rate to therapy with BTA at the peak of the effect: after one course of injections in settings of routine practice, as well as the results of application of modern definition for "response" to treatment with BTA. MATERIAL AND METHODS: In Russia 60 patients with idiopathic CD were included. Patients were classified as «responders¼ according to the following 4 criteria: effect size (improvement by ≥ 25% assessed by TWSTRS); effect duration: ≥ 12 weeks interval between the BTA injection and the day when the patient reported a decrease of clinical effect, indicating the need for repeated treatment; good tolerability of treatment (no treatment-related serious adverse events (AEs) during the study period); patient-reported Clinical Global Improvement (CGI) score is +2 («significant improvement¼) or +3 («very significant improvement¼) at the visits 2 or 3. RESULTS AND CONCLUSION: In the Russian population, patients with a ≥ 25% improvement by TWSTRS scale at visit 2 (peak effect) accounted for 88.3%. Most of patients (81.6%) and physicians (81.7%) evaluated the efficacy of therapy as a «significant improvement¼ or «very significant improvement¼ by CGI. The criterion of the effect duration was achieved in 50% of cases. The BTA therapy was well tolerated (no severe AEs related to treatment) in 98.3% of patients. Overall, 40% of all patients met all the criteria for response to BTA treatment. According to the analysis of the general population, a high degree of response was observed for the effect size (73.6%), tolerability (97.5%) and patient-reported global clinical improvement (69.8%). Subjective assessment of the duration of the effect was achieved in 49.3% of patients, with 28.6% of patients considered as responders. Most patients met three of the four criteria. The proposed multifactorial definition of «response¼ may be of practical use for routine practice.

[Effectiveness of cerebrolysin in hypertensive supratentorial intracranial hemorrhages: results of a randomized triple blind placebo-controled study].

Cerebrolysin was administered to 38 patients with small hypertensive supratentorial intracranial hemorrhages. Cerebrolysin was used intravenous in drops in dosage of 30 ml during 14 days. High effectiveness and good tolerability of the treatment was shown. In the end of treatment, groups receiving cerebrolysin or placebo were statistically significant differed by the total NIHSS score, Bartel index and the Rankin's modified scale. Moreover, a trend to the decrease of intracranial hemorrhage volume was observed in patients treated with cerebrolysin.

[Experience with application of trospium chloride in patients with neurogenic detrusor overactivity].

Overactive bladder (OAB) is observed in such brain diseases as stroke, hypoxic ischemic encephalopathy, Parkinson's disease (PD), multiple sclerosis (MS). Trospium chloride (spasmex) was used in OAB patients with MS (n = 87), stroke (n = 83), encephalopathy (n = 47) and PD (n = 36) in doses from 15 to 45 mg/day in 2 to 36 month courses. The response with minimal side effects was achieved in 94% patients. In addition to basic effects, trospium chloride relieved spastic constipation in patients with stroke, hypersalivation in PD and anal incontinence in MS.

[7-year experience in usage of mirapex in patients with different forms of primary parkinsonism].

The results of mirapex (pramipexol) treatment of 402 patients with Parkinson's disease and juvenile parkinsonism during the period from 6 months to 7 years are summarized. Mirapex was used in monotherapy as well as in combination with levadopa and other antiparkinsonic drugs. The drug was well tolerated and effective in rest tremor, hypokinesia, muscle rigidity and depression, the more pronounced effect being seen at the early stage of the disease. The use of mirapex allows an effective control of motor fluctuations developing during long-term continuous levodopa therapy. The results obtained characterize mirapex as a drug of choice in the treatment of juvenile parkinsonism. In case of a break in mirapex treatment, the recommencement of treatment usually is not accompanied by reduced sensitivity to drug effect.

The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles.

OBJECTIVE: To study the efficacy, safety, and incidence of BtxA antibody formation with repeated treatments with BtxA in post-stroke upper limb muscle spasticity. METHODS: The study was a prospective open label trial. Patients with established post-stroke upper limb spasticity received 1000 units of BtxA (Dysport) into five muscles of the affected arm on study entry. Treatment was repeated every 12, 16, or 20 weeks as clinically indicated. Each patient received a total of three treatment cycles. Efficacy of treatment was assessed using the Modified Ashworth Scale. Patients were assessed on study entry and on week 4 and 12 of each treatment cycle for all safety and efficacy parameters. Blood samples for BtxA antibody assay were taken at baseline and on completion of the trial. RESULTS: Fifty one patients were recruited and 41 of them completed the study. Improvement from the cycle one baseline was observed in all the outcome measures. Mild to moderately severe treatment related adverse events were reported in 24% of cases. There were no serious adverse events. No BtxA antibodies were detected. CONCLUSION: BtxA at a dose of 1000 units Dysport was efficacious in the symptomatic treatment of post-stroke upper limb spasticity. The study suggests that this effect can be maintained with repeated injections for up to at least three treatment cycles, with duration of effect per cycle of between 12 and 20 weeks. BtxA was safe in the dose used in this study and did not induce the formation of detectable levels of neutralising BtxA antibodies.

[Treatment and prevention of cognitive dysfunction in patients with arterial hypertension and atherosclerosis: results of a randomized double-blind placebo-controlled trial of cerebrolysin]. / Lechenie i preduprezhdenie rasstroistv poznavatel'noi funktsii u bol'nykh arterial'noi gipertoniei i aterosklerozom: rezul'taty randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniia tserebrolizina.

AIM: To assess therapeutic and prophylactic effect of large-dose cerebrolysin (15 ml/day for 28 days) in hypertensive and atherosclerotic patients with cognitive disorders. MATERIAL AND METHODS: Cerebrolysin was given annually (15 ml/day for 28 days) for 2 years to 42 patients in a randomized double-blind placebo-controlled study. The effect was stated by clinical status, neuropsychological and neurophysiological data. RESULTS: In mild disturbances of cognitive functions in patients with arterial hypertension and atherosclerosis courses of cerebrolysin with one-year interval produce stable improvement of subjective status, productivity of memory, attention and thinking which persist for at least a year after the course. The clinical data agree with positive trend in neurophysiological parameters of cognitive component of the response of evoked potentials P-300. CONCLUSION: A course of 28-day annual treatment with cerebrolysin (15 ml/day) of patients with mild defects of cognitive functions stabilizes the process, leads to regression of cognitive disorders predicting vascular dementia.

Pharmacokinetics and tolerability of iopromide 240 after lumbar myelography.

OBJECTIVE: To evaluate the pharmacokinetics and tolerability of iopromide 240 mg iodine/mL after intrathecal administration. METHODS: Eleven patients with an indication for lumbar myelography received 10 mL iopromide 240 in an open, prospective, single-center study. All patients were followed 72 hours after the procedure and remained in the hospital. Urine was sampled from before the myelography up to 72 hours after the procedure in stages (range, 0-6, 6-12, 12-24, 24-48, and 48-72 hours). Iodine plasma levels were determined before and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 9 hours, 12 hours, and 24 hours after the administration of iopromide 240. Vital signs were measured at baseline, before, and 1 and 24 hours after the procedure. Physical and neurologic examinations were performed in all patients at baseline and at the end of the study period; all adverse events were recorded. The results were subject to pharmacokinetic analysis using compartment model-independent and -dependent methods. RESULTS: Ten of 11 patients had measurable iodine plasma levels. After a lag time of approximately 0.6 hours (mean value), maximum iodine concentrations of 45% of the administered dose per total plasma volume were observed after 3.8 hours. Plasma half-lives ranged from 3.0 to 60.5 hours (model-independent methods) with a mean of 14.9 hours and a standard deviation of 17.0 hours. Using curve fitting with an open one-compartment model revealed good agreement with the model-independent methods (half-life 17.3 hours). The recovery of iodine in urine in the 72-hour period was 78%+/-15% (range, 53%-94%) as a result of an undeterminable loss of urine in some patients and prolonged half-lives in two patients. Only one patient had adverse events 24 hours after myelography. CONCLUSIONS: After lumbar myelography, iopromide 240 is almost completely excreted renally within 72 hours, with a prolonged half-life as a result of the route of administration. The kinetics of iopromide 240 after intrathecal administration are characterized by a prolonged half-life. The safety of the contrast medium was confirmed.