One of the modern components of complex rehabilitation of patients with spasticity is the use of botulinum toxin type A (BTA) preparations. International experience with the use of botulinum therapy in children spans more than 30 years. Abobotulinum toxin A has been used to treat spasticity since 1994. Clinical studies have shown the high efficacy of abobotulinumtoxin A in relieving spasticity of the lower and upper extremities in cerebral palsy (CP) and other disorders, which is associated with a significant increase in muscle tone, thereby increasing motor skills and achieving individual patient goals. The article presents a consensus of Russian experts on the approach to selecting target muscles and calculating the dose of abobotulinumtoxin A in multilevel injections, and discusses the planning of repeat injections, ethical and legal aspects of botulinum therapy in children, the combination of botulinum therapy with other methods of correcting spasticity in CP, the use of BTA in dystonia and sialorrhea, and factors potentially influencing the effectiveness of botulinum therapy. This consensus summarizes the views of Russian experts on creating an injection protocol depending on individual clinical data and treatment goals, which can be used as a guide for practical work.
OBJECTIVE:To evaluate the most typical target muscles and dosages for the first and repeated botulinum toxin A (BTA) injections in cerebral palsy (CP) patients with severe motor deficit - GMFCS IV-V.MATERIAL AND METHODS:A retrospective analysis of 677 protocols of the first and repeated Abobotulinumtoxin A (AboA) injections in 333 patients with CP GMFCS IV and V, aged 1 to 18 years, was carried out.RESULTS:Ninety-seven percent of patients received multilevel injections. In the lower extremities the most typical target muscles were: m.gracilis - 221 (66.4%) patients, hip adductors - 164 (49.2%), medial hamstring - 144 (43.2%). In the upper extremities the most typical muscles were: m.pronator teres - 237 (71.2%) patients, m.biceps brachii+m.brachialis - 197 (59.2%). The total dosages of AboA and dosages for every target muscle were calculated. Several patients required high dosages (more than 30 U/kg of AboA). Higher dosages per kg were used in younger children and for repeated injections. The age-related evolution of spastic patterns was described. Adverse events were observed in 36 cases (5.3% of all injections).CONCLUSION:The majority of patients with GMFCS IV-V required multilevel BTA injections in high dosages, especially in young age. Described selection of target muscles and dosages of AboA could be taken into account as a practical experience and reference for the BTA therapy in GMFCS IV-V patients.
Spasticity treatment is one of the key aspects of the contemporary cerebral palsy (CP) rehabilitation that influences on the effectiveness of other methods. The paper presents the first Russian document that unites the recommendations for the BTA treatment of CP and could be used as the guideline for the multilevel injections. The Russian consensus on the multilevel botulinum toxin A (BTA) treatment of spastic CP is based on the international data and the results of national studies. The authors describe typical CP spasticity patterns in the upper and lower extremities, give recommended intervals for the BTA (Abobotulinum toxin A) dosages for the whole injection procedure and for the separate muscles. The method of dosage calculation for functional segments is also described. Attention is paid to the frequency, optimal intervals between the repeated injections and the whole duration of BTA treatment. The authors discuss effectiveness and safety of BTA, factors that potentially influence the results of the injections, including ultrasound and electromyography control, and indications for the continuation and termination of treatment.
Hypoxic-ischemic brain lesions in children are the main environmental (non-genetic) factor in forming severe neurological pathology with subsequent disability. Scientists see the improvement of therapeutic approaches in acute phase of the disease as a main way to reduce the severity of neurologic complications. Due to the achievements in neuroscience in the field of perinatal hypoxicischemic injury mechanisms, three energy phases of pathologic events deployment were identified: primary (up to 6 hours from the lesion), secondary (6 to 24–48 h after the lesion) and distal tertiary (during few weeks, months). At the same time, necrosis, apoptosis, glutamate excitotoxicity, oxidative stress, inflammation, angiogenesis and neurogenesis make up separate links of destruction process. On the basis of new data on the pathogenesis of the disease, scientists from different countries have already offered modern treatment methods for perinatal hypoxic-ischemic injury with erythropoietin, allopurinol, melatonin, N-acetylcysteine, magnesium sulphate, albumin, -interferon, as well as with the help of controlled hypothermia, xenon, the use of stem cells, etc. This article presents a review of new data on pathogenesis and promising treatment methods for perinatal hypoxic-ischemic injuries.
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.
Botulinum toxin type A (BoNT-A) is used in cerebral palsy (CP) for more than 20 years. Nevertheless, the unified protocol of injections and doses does not exist by now. The correct selection of target muscles for BoNT-A injections is based on the experience of the doctor, detailed analysis of neurological and orthopedic status of the patient, standard scales to evaluate motor potential of the patient. The article represents the detailed review of international clinical trials for multi-level use of BoNT-A in CP and recommendations on doses calculation. Based on our own observations of efficacy and safety of single-used doses of Botox we present the recommended dose ranges for upper and lower limb that led to clinically significant decrease of spasticity with no undesirable weakness. The review of clinical cases presents the doses per targeted muscle and total doses we used, they are advisory in nature.
The article provides general information on botulinum therapy in treating spastic forms of cerebral palsy; a review of modern botulinum toxin A drugs’ injection precision control methods at spasticity and other pathologic states is given; advantages and disadvantages of each injection control method are analyzed in detail. Special attention is paid to the substantiated choice of the injection control method in pediatric practice; muscles of the highest degree of complexity for botulinum therapy at spastic forms of cerebral palsy are described. The authors’ observations and results of applying ultrasound botulinum toxin A drugs’ injection control at different spasticity patterns in children are given.
Despite the fact that there are the researches testifying to activation of congenital (nonspecific) and got (adaptive, specific) immunity in Central Nervous System Perinatal Damages, interrelations between blood sera immunological indicators and clinical lines of Central Nervous System Perinatal Damages are studied now insufficiently. In our work the analysis of interrelations between a number of immunological indicators (the activity of leucocyte elastase (LE) and 1-proteinase inhibitor (α1-PI), the rates of autoantibodies (aAB) to nerve tissue proteins) and psychomotor development of children with consequences of Central Nervous System hypoxic-ischemic Perinatal Damages has been carried out. It is revealed that in this pathology activation of the congenital and got immunity takes place; the congenital immunity activation degree (on LE activity) back correlates with severity of psychomotor development disorders, activity α1-PI directly correlates with a psychomotor development point of children, i.e. its lowered activity is the adverse diagnostic factor; joining of autoimmune reactions (increased rates of aAB to nerve tissue proteins) characterizes the heaviest variants of psychomotor development retardations. It is shown also that pre-term infants have lower point of psychomotor development, and also more patients of this group have low α1-PI activity and the raised levels of aAB in comparison to full-term infants.Key words: children, perinatal damages of central nervous system, psychomotor development, congenital immunity, leucocyte elastase, α1-proteinase inhibitor, autoimmune reactions.
Despite the fact that there are the researches testifying to activation of congenital (nonspecific) and got (adaptive, specific) immunity in Central Nervous System Perinatal Damages, interrelations between blood sera immunological indicators and clinical lines of Central Nervous System Perinatal Damages are studied now insufficiently. In our work the analysis of interrelations between a number of immunological indicators (the activity of leucocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), the rates of autoantibodies (aAB) to nerve tissue proteins) and psychomotor development of children with consequences of Central Nervous System hypoxic-ischemic Perinatal Damages has been carried out. It is revealed that in this pathology activation of the congenital and got immunity takes place; the congenital immunity activation degree (on LE activity) back correlates with severity of psychomotor development disorders, activity α1-PI directly correlates with a psychomotor development point of children, i. e. its lowered activity is the adverse diagnostic factor; joining of autoimmune reactions (increased rates of aAB to nerve tissue proteins) characterizes the heaviest variants of psychomotor development retardations. It is shown also that pre-term infants have lower point of psychomotor development, and also more patients of this group have low α1-PI activity and the raised levels of aAB in comparison to full-term infants.
Botulinum toxin type A (BoNT-A) is used in cerebral palsy (CP) for more than 20 years. Nevertheless, the unified protocol of injections and doses does not exist by now. The correct selection of target muscles for BoNT-A injections is based on the experience of the doctor, detailed analysis of neurological and orthopedic status of the patient, standard scales to evaluate motor potential of the patient. The article represents the detailed review of international clinical trials for multi-level use of BoNT-A in CP and recommendations on doses calculation. Based on our own observations of efficacy and safety of single-used doses of Botox we present the recommended dose ranges for upper and lower limb that led to clinically significant decrease of spasticity with no undesirable weakness. The review of clinical cases presents the doses per targeted muscle and total doses we used, they are advisory in nature.
Experimental uveitis is characterized by a pronounced lipid peroxidation (LPO) in damaged tissues of eye, which is complicated by reduced activity of the antioxidant enzymes, SOD and catalase. The intensification of LPO was also found in blood serum and hepatic tissue. However, hepatic lipid peroxidation was accompanied by compensatory increase of catalase activity. The activity of antioxidant defence enzymes decreased in blood, whereas catalase was activated in hepatic tissue. The therapeutic effect was accompanied by a decrease of LPO products and increase of activity of the antioxidant enzymes in all tissues. Treatment of uveitis with gentamycin and, especially, perftoran reduced inflammatory events.
Catecholamines and DOPA excretion and televant levels in blood were measured in 17 patients with facial paraspasm and in 24 healthy subjects. The findings gave evidence for sympathetic-adrenal system adrenal activation and more intensive catecholamine metabolism in patients, especially marked in those with generalised facial hyperkinesia.
: Blood hormones and urinary excretion of corticosteroids were measured in 39 parkinsonian patients receiving chemotherapy with adjuvant 3-week course of verospiron (50-100 mg/day). The latter promoted normalization of endocrine and clinical statuses in the majority of the patients. It is suggested that the response may be obtained via neuropeptide systems of the brain.
Catecholamines excretion has been analyzed in 36 patients suffering from parkinsonism and in 30 normal subjects. Curable patients demonstrated the same proportion of epinephrine and norepinephrine/DOPA excretion as normal subjects did. In resistant to treatment subjects and in unlikely curable the above coefficients were significantly larger. It is suggested that enhanced activity of peripheral sympathoadrenal system may serve a factor of low response to medication.
The authors found changes in the function of the adrenals in parkinsonism, which were expressed in the form of elevated excretion of aldosterone and diminished excretion of hydrocortisone. The use of veroshpiron led to a certain normalization of adrenal function and to activation of the sympatho-adrenal system. The study of the clinical efficacy of veroshpiron administered for 20 days in a daily dose of 50-100 mg to 56 patients with parkinsonism showed improvement of a varying degree in 87.5% of patients. A 20-day course of veroshpiron resulted in regression of approximately 1/3 of the main symptoms of parkinsonism with the improvement persisting for several months.
On withdrawal of L-DOPA-containing drugs the blood serotonin content decreased in parkinsonism patients irrespective of form and etiology of the disease. L-DOPA-containing drugs caused the blood serotonin levels to rise. Substantial correlations of the blood serotonin levels and clinico-physiologic indices were found mostly in postencephalitic parkinsonism.
Content of serotonin was studied in blood of 81 patient with parkinsonism and of 31 practically healthy person. Content of serotonin was distinctly decreased in blood of the patients with parkinsonism. With ageing concentration of the amine was increased in blood of the patients and decreased in control group.