Ботулинотерапия в лечении дистонического сколиоза при генерализованной дистонии (клиническое наблюдение)

Dystonic scoliosis as one of the forms of generalized dystonia is a highly disabling form of dystonia, which can lead to damage to internal organs (lungs, heart) and the peripheral nervous system, including the spinal cord. Almost always, those muscles that are involved in the formation of a dystonic posture in generalized dystonia have not been studied in terms of the effectiveness of treatment with botulinum toxin type A and are not reflected in the instructions. As a result, there is no understanding of the general motor interaction with differentiation into targeted and non-targeted muscles, administration doses and control methods.The aim of the work was to evaluate the efficacy and tolerability of high doses of botulinum toxin type A in dystonic scoliosis, as well as to present the introduction of botulinum toxin type A using ultrasound and electromyographic control. We have described a clinical case of a 19-year-old patient suffering from generalized dystonia with S-shaped dystonic scoliosis of the III degree. Deep brain stimulation was recommended as a treatment for the patient. During the waiting period for the timing of the operation, we attempted symptomatic therapy using the drug incobotulotoxin A. Over the next year and a half, 700 units of botulinum toxin type A were administered under ultrasound and electromyographic control every 3–4 months. As a result, treatment of trunk dystonia in the patient during the observation period led to a clinically significant decrease in the degree of curvature (from 37° to 27°, from III to II degree of scoliosis) in the absence of undesirable effects of the drug, including generalized muscle weakness. According to the repeated conclusion of the council of neurosurgeons, surgical intervention is not indicated for the patient due to the positive effect of the introduction of botulinum toxin type A.Дистонический сколиоз как одна из форм генерализованной дистонии является высокоинвалидизирующей формой дистонии, которая может приводить к повреждению внутренних органов (легких, сердца) и периферической нервной системы, включая спинной мозг. В большинстве случаев мышцы, которые участвуют в формировании дистонической позы при генерализованной дистонии, исследуются мало в плане эффективности лечения препаратами ботулинического токсина типа А и, как следствие, не отражены в инструкциях. В результате отсутствует методическое понимание общего двигательного взаимодействия с дифференцировкой на таргетные и не таргетные мышцы, дозы введения и методов контроля.Цель настоящей работы – оценить эффективность и переносимость высоких доз ботулинического токсина типа А при дистоническом сколиозе, а также представить возможности введения ботулинического токсина типа А с использованием ультразвукового и электромиографического контроля.Нами описан клинический пример пациента 19 лет, страдающего генерализованной дистонией с С-образным дистоническим сколиозом III степени. В качестве лечения пациенту была рекомендована глубокая стимуляция головного мозга. В период ожидания сроков операции нами была предпринята попытка симптоматической терапии с использованием препарата инкоботулотоксина А. В течение последующих полутора лет введение 700 ЕД ботулинического токсина А проводили под ультразвуковым и электромиографическим контролем каждые 3–4 мес. В результате у пациента за период наблюдения лечение дистонии туловища привело к клинически достоверному снижению градуса искривления (с 37 до 27°, с III до II степени сколиоза) при отсутствии нежелательных явлений действия препарата, включая генерализованную мышечную слабость. Согласно повторному заключению консилиума нейрохирургов, оперативное вмешательство пациенту не показано ввиду положительного эффекта от введения ботулинического токсина типа А

Anti-drug Antibody Responses Impair Prophylaxis Mediated by AAV-Delivered HIV-1 Broadly Neutralizing Antibodies

Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly compare the performance of the IgG1-Fc and the IgG2-Fc domains in a prophylactic setting, we compared AAV1 expression of rhesus IgG1 and IgG2 forms of four anti-HIV bNAbs: 3BNC117, NIH45-46, 10-1074, and PGT121. Interestingly, IgG2-isotyped bNAbs elicited significantly lower ADA than their IgG1 counterparts. We also observed significant protection from two SHIV-AD8 challenges in macaques expressing IgG2-isotyped bNAbs, but not from those expressing IgG1. Our data suggest that monoclonal antibodies isotyped with IgG2-Fc domains are less immunogenic than their IgG1 counterparts, and they highlight ADAs as a key barrier to the use of AAV1-expressed bNAbs

Electrical, Hemodynamic, and Motor Activity in BCI Post-stroke Rehabilitation: Clinical Case Study

The goal of the paper is to present an example of integrated analysis of electrical, hemodynamic, and motor activity accompanying the motor function recovery in a post-stroke patient having an extensive cortical lesion. The patient underwent a course of neurorehabilitation assisted with the hand exoskeleton controlled by brain-computer interface based on kinesthetic motor imagery. The BCI classifier was based on discriminating covariance matrices of EEG corresponding to motor imagery. The clinical data from three successive 2 weeks hospitalizations with 4 and 8 month intervals, respectively were under analysis. The rehabilitation outcome was measured by Fugl-Meyer scale and biomechanical analysis. Both measures indicate prominent improvement of the motor function of the paretic arm after each hospitalization. The analysis of brain activity resulted in three main findings. First, the sources of EEG activity in the intact brain areas, most specific to motor imagery, were similar to the patterns we observed earlier in both healthy subjects and post-stroke patients with mild subcortical lesions. Second, two sources of task-specific activity were localized in primary somatosensory areas near the lesion edge. The sources exhibit independent mu-rhythm activity with the peak frequency significantly lower than that of mu-rhythm in healthy subjects. The peculiarities of the detected source activity underlie changes in EEG covariance matrices during motor imagery, thus serving as the BCI biomarkers. Third, the fMRI data processing showed significant reduction in size of areas activated during the paretic hand movement imagery and increase for those activated during the intact hand movement imagery, shifting the activations to the same level. This might be regarded as the general index of the motor recovery. We conclude that the integrated analysis of EEG, fMRI, and motor activity allows to account for the reorganization of different levels of the motor system and to provide a comprehensive basis for adequate assessment of the BCI+ exoskeleton rehabilitation efficiency

EFFICACY OF COMPLEX NEUROREHABILITATION OF PATIENTS WITH A POST-STROKE ARM PARESIS WITH THE USE OF A BRAIN-COMPUTER INTERFACE+EXOSKELETON SYSTEM

Background: Rehabilitation of patients with poststroke motor disorders with the use of a brain-computer interface (BCI)+exoskeleton may raise the rehabilitation to a  new high-tech level and allow for an effective correction of the post-stroke dysfunction. Aim: To assess the efficacy of BCI+exoskeleton procedures for neurorehabilitation of patients with post-stroke motor dysfunction. Materials and methods: The study included 40 patients with a history of cerebral stroke (mean age 59±10.4 years, 26 male and 14 female). Thirty six of them had had an ischemic stroke and 4, a hemorrhagic stroke from 2 months to 4 years before the study entry. All patients had a various degree post-stroke hemiparesis predominantly of the arm. The main group patients (n=20), in addition to conventional therapy, had 10  sessions (3  times daily) of BCI+exoskeleton. The BCI recognized the hand ungripping imagined by the patient and, by a  feedback signal, the exoskeleton exerted the passive movement in the paretic arm. The control group patients (n=10) had 10  BCI+exoskeleton sessions without imaginary movements, and the exoskeleton functioned in a  random mode. The comparison group included 10  patients who received only standard treatment. Results: At the end of rehabilitation treatment (day 14), all study groups demonstrated an improvement in the function of the paretic extremity. There was an improvement of functioning and daily activities in the main group, compared to the control and the comparison groups: the change in the modified Rankin scale score was 0.4±0.1, 0.1±0.1  and 0±0.2 (p<0.05), in the Bartel scale score, 5.6±0.8, 2.3±0.3 and 1±0.2 (p<0.001), respectively. In the BCI+exoskeleton group the motor function of the paretic arm assessed by the ARAT scale, improved by 5.5±1.3  points (2.4±0.6  points in the control group and 1.9±0.7  in the comparison group, р<0.05), and as assessed by the Fugl-Meyer scale, by 10.8±1.5 points (3.8±1.05 points in the comparison group, p<0.001). Conclusion: Rehabilitation of patients with post-stroke paresis with the use of BCI+exoskeleton led not also to a decrease in neurological deficit and an improvement of the paretic arm motor function, but also improved parameters of daily activities. Further studies of the effects of BCI+exoskeleton rehabilitation procedures on the course of motor function restoration are planned