Neuromuscular Diseases

Aim. To present the authors’ experience in implementing a frameless stereotactic infusion technique of a gene preparation using an adeno-associated vectored virus into the subcortical structures of the brain in children with aromatic L-amino acid decarboxylase deficiency (AADCd), with an emphasis on technical and organizational aspects.

Materials and methods. From November 2024 to December 2025, six bilateral infusions of eladocagen exuparvovec (Upstaza^®) were administered into the putamen of children with genetically confirmed AADCd in the Department of Pediatric Neurosurgery of the Russian Children’s Clinical Hospital. The key stages of patient selection, regulatory support, preoperative planning based on brain magnetic resonance imaging data, features of frameless navigation, the Z-shaped convection-enhanced infusion technique, and measures for preventing intra- and postoperative complications are described. The analysis of clinical outcomes is deliberately not presented in this work and is planned for a separate publication after increasing the sample size and follow-up observation.

Results. In all 6 cases, accurate drug delivery to the putamen was ensured in accordance with preoperative planning, and no intraoperative complications were observed. Early postoperative magnetic resonance imaging monitoring revealed no clinically significant hemorrhagic or ischemic brain damage. In all cases, improvements in motor and autonomic symptoms of varying severity were noted during the first months of follow-up.

Conclusion. The presented experience demonstrates the technical feasibility and safety of frameless stereotactic gene therapy for AADCd in children in a Federal Center setting. The proposed method can serve as the basis for a national treatment protocol for AADCd and the establishment of a reference center for gene therapy for central nervous system diseases.

Background. Myasthenia gravis (MG) is a chronic autoimmune disease that significantly affects patients’ quality of life. Studying the regional characteristics of MG is important for optimizing medical care.

Aim. To study the socio-demographic and clinical-functional characteristics of patients with MG in the Republic of Bashkortostan.

Materials and methods. A cross-sectional study was conducted based on data from the Republican Medical Information and Analytical System as of 01.01.2024. Data from 249 patients diagnosed with MG (G70.0) were analyzed.

Results. Data from 249 patients with MG were analyzed. Women (70.3 %) and individuals over 50 years of age (69 %) predominated among them. The mean age of disease onset was 43.1 years. The generalized form of MG was diagnosed in 86.7 % of patients and was significantly more common in women. Approximately half of the patients had a disability. During the year, 63.4 % of patients visited a neurologist on an outpatient basis, and 52.2 % received inpatient treatment. All patients received pyridostigmine bromide, in combination with glucocorticoids – 66.6 %, and with cytostatics – 2.8 %. Thymectomy was performed in 12.4 % of patients. High comorbidity was noted: on average, there were 3 comorbid conditions per patient.

Conclusion. The study results demonstrate the high medical and social significance of MG in the Republic of Bashkortostan. Enhancement of outpatient medical care for patients with myasthenia gravis in the Republic of Bashkortostan and implementation of more personalized treatment approaches are required.

Quadripulse stimulation (QPS) is a relatively new and highly promising repetitive transcranial magnetic stimulation protocol. QPS is based on the application of bursts, consisting of 4 monophasic stimuli with a very short interstimulus interval (5 or 50 ms, QPS 5 and QPS50, respectively), which are repeated every 5 seconds. Long-term neuromodulating effects of QPS protocols are bi-directional depending on interstimulus interval: QPS5 increases the excitability of motor cortex while QPS50 decreases it. The main advantage of QPS protocols is a high reproducibility of their effects, which exceeds that of other repetitive transcranial magnetic stimulation protocols. This review discusses the physiological effects and possible mechanisms for inducing neuroplasticity by QPS protocols. Special attention is paid to QPS application in clinical practice both for therapeutic neuromodulation and development of new biomarkers of functional brain state. Available QPS safety data are provided and previous works limitations as well as directions for further studies are analyzed.

Aromatic L-amino acid decarboxylase deficiency is a severe, rare, genetic disorder of the neurotransmitter group caused by mutations in the DDC gene, characterized by impaired production of neurotransmitters such as dopamine, serotonin, norepinephrine, and adrenaline. As a result of their deficiency, children develop and rapidly progress to such basic clinical manifestations as gross delay in motor and psychore-speech development, episodes of oculogyric crises (episodically occurring con-current deviation of the eyes up, laterally and/or down lasting from several minutes to several hours) of varying severity and frequency, as well as a whole range of autonomic symptoms. Currently gene therapy is used in the Russian Federation for the treatment of this disease. In this regard, the problem of establishing/verifying a diagnosis for the treatment of patients with aromatic L-amino acid decarboxylase deficiency becomes particularly relevant.