Background. Expansion-based autosomal dominant spinocerebellar ataxias (ADSСA-E) represent a clinically and genetically heterogeneous group of inherited neurodegenerative disorders characterized by cerebellar atrophy. According to global population data, they account for approximately 61 % of all autosomal dominant spinocerebellar ataxias. The number of nucleotide repeats is a key determinant of penetrance, expressivity, and age of onset, necessitating precise molecular genetic analysis. Significant differences in the structure of ADSСA-E across populations underscore the need for regional studies. Aim. Analysis of the molecular structure and frequency of ADSCA-E in a sample of Russian patients with cerebellar ataxias. Materials and methods. DNA samples from 1272 patients with clinical signs of ataxia (2017–2024) were analyzed. The number of repeats in the ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATXN10, PPP2R2B, NOP56, and ATXN8OS genes was determined using fluorescent polymerase chain reaction and fragment analysis. The age at referral to the laboratory was considered an indirect marker of disease aggressiveness. Statistical analysis was performed using GraphPad Prism 10. Differences were considered statistically significant at p 0.05. Pearson’ correlation coefficient was used to calculate correlation. Results. A pathological expansion was identified in 102 (8 %) patients. The most frequent form was spinocerebellar ataxia (SCA) type 1 (62.7 %), followed by SCA type 2 (17.6 %), SCA type 3 (5.9 %), and SCA type 6 (3.9 %); other types were rare. A case of combined SCA type 1 and SCA type 8 mutations was recorded in one patient. For SCA type 1 and SCA type 2, a significant negative correlation was established between the expansion size and the age at referral (p 0.0001; r = –0.6839 and –0.8838, respectively). Conclusion. Data on the frequency and spectrum of ADSCA-E in the Russian Federation, including rare forms, were obtained. The prognostic significance of the repeat number was confirmed, and the necessity of molecular genetic testing, taking into account regional disease prevalence patterns, was emphasized.
Biallelic pentanucleotide AAGGG expansion in the RFC1 gene is the molecular basis of сerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), one of the most common causes of late-onset ataxias. The phenotypic spectrum of RFC1-associated pathology has significantly expanded in recent years: it includes motor neuron disease, parkinsonism, cognitive impairment, and isolated manifestations of CANVAS symptoms (polyneuropathy, bilateral vestibulopathy, and chronic cough). This review summarizes current information on the phenotypic diversity of RFC1-associated diseases, which changes the understanding of diagnostic tactics and differential diagnostic algorithms for CANVAS and a number of other forms of neurodegenerative pathology.
Hereditary neuromuscular disorders (NMDs) comprise a clinically and genetically heterogeneous group of conditions characterized by the involvement of the peripheral nervous system and skeletal muscles. This work presents a literature review focusing on brain neuroimaging findings in hereditary NMDs detected by magnetic resonance imaging. The aim of this work was to describe and synthesize current data on brain magnetic resonance imaging abnormalities across various hereditary NMDs, based on a literature review and a clinical case series, and to evaluate potential clinico-radiological correlations. A literature search was conducted in the PubMed database from 1984 to 2025 July using keywords including (white matter lesion) AND (myotonic dystrophy), (white matter lesion) AND (hereditary neuropathy), (white matter lesion) AND (Charcot–Marie–Tooth), (white matter lesion) AND (muscular dystrophy), (white matter lesion) AND (myasthenic syndrome), and (white matter lesion) AND (motor neuron disease). A total of 107 publications were included in the final review. A clinical case series with magnetic resonance imaging data is also presented, including Charcot–Marie–Tooth disease type 1X, myotonic dystrophy types 1 and 2, merosin-deficient congenital muscular dystrophy, and limb-girdle muscular dystrophy type 23. The reviewed literature indicates that brain magnetic resonance imaging can have both diagnostic and prognostic clinical significance in some hereditary NMDs, especially in myotonic dystrophies, merosin-deficient muscular dystrophy, and Charcot–Marie–Tooth disease type 1X. The presented case series illustrates the variety of magnetic resonance imaging patterns and their association with clinical manifestations, underscoring the importance of integrating neuroimaging into the diagnostic workup for hereditary NMDs.
Duchenne muscular dystrophy is an inherited X-linked disorder characterized by progressive muscle wasting, loss of mobility, and death from cardiorespiratory complications. The absence of functional dystrophin triggers a cascade of pathological events in muscles including chronic inflammation, impaired regeneration, and substitutive fibroadipose degeneration. New approaches aimed at restoring or replacing dystrophin synthesis increased the delay in loss of ambulation achieved with standard corticosteroid therapy, but high demand for a different mechanism of action regardless of the DMD mutation variant remains. Givinostat is the first histone deacetylase inhibitor for Duchenne muscular dystrophy treatment, showing a positive myoprotective effect on key pathogenetic consequences of dystrophin dysfunction regardless of the mutation in the DMD gene. In clinical studies, givinostat improves motor function, reduces inflammatory infiltration and fibroadipose degeneration of muscle tissue, and allows to delay the loss of ambulatory function by almost 3 years.
Background. The main clinical manifestation of hereditary cerebellar ataxias is a progressive loss of motor coordination and balance, leading to a reduced quality of life increased risk of falls. Balance impairments in patients are assessed using both general clinical and specialized scales, which allow for a detailed characterization of symptoms. Aim. To investigate the clinical and stabilometric parameters of balance and risk factors for falls in patients with hereditary cerebellar ataxias. Materials and methods. The study included 38 patients with hereditary cerebellar ataxias and 22 healthy volunteers in the control group. To assess balance impairments, mobility, and fall risk, general clinical scales (the Timed Up and Go (TUG) test, the Berg Balance Scale (BBS), the 10-meter walk test) and specific scales (the Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS)) were used. Stabilometric parameters were recorded using the ST-150 platform. Based on the clinical scales, patients were stratified according to their risk of falls. Results. When stratifying patients by fall risk, the use of general clinical scales led to different risk level classifications: according to the TUG test, the majority of patients (65 %) had a low risk, while according to the BBS, 76 % were classified as high-risk. Gait analysis confirmed a decrease in comfortable and fast walking speed with an increase in fall risk, which was more pronounced when stratified by the TUG test, reflecting dynamic balance impairments. The use of specific scales (SARA and ICARS) established that ataxia symptoms worsen with an increase in fall risk, especially when grouped by the TUG test, which better reflects the clinical features of patients associated with fall risk. Stabilometric analysis revealed significant changes in static and static-dynamic balance parameters even in patients with no fall risk according to the TUG test, and also showed that the BBS is the most sensitive to these impairments. Conclusion. The combined use of the BBS and the TUG test allows for a comprehensive assessment of balance disorders and enables the personalization of rehabilitation and fall prevention programs for this patient group.
Background. Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the nervous system, the prevalence of which varies considerably in different regions of the world. Epidemiologic studies of ALS in the Russian Federation are scarce.Aim. To analyze the epidemiological features of ALS in the Republic of Bashkortostan (RB) according to the data of the unified state information system in the field of health care and clinical characteristics according to the hospital register for the period 2013–2024.Materials and methods. A retrospective analysis of electronic medical records of all patients living in the RB who were diagnosed with G12.2 according to the 10th revision of the International Classification of Diseases within analyzed period was performed. The study of clinical characteristics of patients with ALS was done using data from the hospital registry, which was maintained since 2013.Results. The primary incidence of ALS in RB increased from 0.7 to 1.1–1.3 cases per 100,000 population over the period 2013–2024. The overall incidence of ALS for this period increased more than 3-fold, from 0.8 to 2.7 cases per 100 thousand population. The first manifestations of the disease were more often noted at the age of 53–66 years, among patients prevailed rural residents (59.5 %), people of physical labor (48.3 %). Men were more often suffered from ALS in the group with onset before the age of 45 years (p = 0.028), women more often had bulbar form of the disease (p = 0.046). The diagnosis was established on average one year after the development of the first symptoms of the disease.Conclusion. There was an increase in the incidence of ALS over 2012–2024, which probably reflects improved detection of the disease in the RB. Future studies should clarify the role of environmental and biological factors in the development of ALS.
Background. The polyetiology of dry eye syndrome requires a whole range of diagnostic measures. In turn, to verify the subtype of dry eye syndrome – burning eye syndrome – it is necessary to record characteristic changes in nerve fibers and the lipid layer of the tear film. This can be done using such methods as laser scanning confocal microscopy, thiascopy and tear osmolarmetry.Aim. To determine the role of instrumental research methods in the diagnosis of burning eye syndrome.Materials and methods. 31 patients (14 men, 17 women) aged 18–45 years were examined, the average age of the subjects was 31 ± 3 years. The patients complained of dryness, burning, discomfort during visual work, and eye pain. The control group was formed from 28 healthy volunteers matched for gender and age. The exclusion criteria from the study were: clinical signs of blepharitis and dysfunction of the meibomian glands, rheumatological (rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, scleroderma) and oncological diseases. In addition to a functional ophthalmological examination, all patients underwent laser scanning confocal microscopy of the cornea on an HRT III device with a Cornea Rostock corneal module to assess the condition of the epithelium and nerve fibers of the cornea. Thiascopy was used to assess the lipid layer of the tear film.Results. In the group of patients with burning eye syndrome, the greatest changes in the structure of the nerve fiber were statistically reliably recorded, in comparison with patients with dry eye syndrome and volunteers. The tear osmolarity indicators were close to the results of the control group, no statistically significant difference was recorded between them. According to the results of tiascopy, changes in the lipid layer of the tear film were pronounced: zones with a thickness of more than 0.5 μm and 0.27–0.5 μm averaged 0.04 % and 2.2 %, respectively.Conclusion. The implementation of specialized instrumental methods and the combined assessment of their results play a decisive role in the diagnosis of burning eye syndrome, which allows for the prescription of appropriate treatment.
Aim. To present Kinematic 4, a software tool designed for automated analysis of reach-to-grasp and object transport movements using data obtained from motion capture systems.Materials and methods. The software was developed in Python and implements algorithms for automatic detection of key temporal events in motor actions. Initially validated in MATLAB, the algorithmic framework was adapted into a cross-platform desktop application with a graphical user interface. Kinematic 4 processes coordinate data from markers placed on the thumb, index finger, wrist, object, and specialized glasses with a movable shutter. The program identifies six critical time points: experiment onset, hand lifting, finger opening, maximum grasp aperture, object lifting, and object placement.Results. Comparison between results obtained using Kinematic 4 and those generated by the original MATLAB script demonstrated full consistency. The software was successfully validated on experimental datasets and showed high stability. Its user-friendly interface and automated workflow make it a reliable and reproducible tool for both research and clinical applications.Conclusion. Kinematic 4 can be effectively used for assessing upper-limb movements in neuroscience and clinical contexts, including the diagnosis of motor impairments and monitoring of recovery dynamics. Future development may include integration with other biosignals and machine learning modules for predictive analytics.
Aim. Using factor analysis, identify and rank the parameters potentially influencing the course of amyotrophic lateral sclerosis (ALS) according to their significance.Materials and methods. A prospective cohort study of 70 patients with ALS diagnosed according to the Gold Coast criteria (2020) was performed. We studied basic socio-demographic indicators, education and social status, geography of living, anamnestic data about the disease (appearance of the first symptoms, onset, etc.), clinical picture (symptoms in the main muscle groups), progression of ALSFRS-R score, environmental risk factors (including 23 features, presented in gradation from the lowest to the highest expression).Results. The mean age of the patients was 60.62 ± 10.2 years. The predominant proportion of patients was female,61.4 % (n = 43), the proportion of males was 38.6 % (n = 27). The mean time from onset of symptoms to inclusion in the study and questionnaire was 12 months (95 % confidence interval 9.00–21.50). Low level of education, onset from bulbar symptoms and neck muscle involvement, severity of oral automatism reflexes, difficulty in walking and standing, contact with heavy metals, occupational sports and high stress level were correlated with rapid progression of ALS, while high level of physical activity, frequent caffeine consumption, antioxidant intake, vitamin D deficiency were observed in slow progression of ALS.Conclusion. Our data confirm that ALS is a clinically and pathogenetically heterogeneous disease, whose rate of progression is influenced by a wide range of clinical, anamnestic, and environmental factors.
We present a clinical case of suppression of cervical segmental motor evoked potential in a child with post anoxic encephalopathy. We performed a dynamic examination of a 4-year-old female patient after acute post hypoxia (freshwater drowning) using single-pulse magnetic stimulation, magnetic resonance tractography with reconstruction of the corticospinal tract from the primary motor cortex and supplemental area, segmentation and morphometry of brain. Post hypoxic damage in a 4-year-old child resulted not only in the loss of cortical motor evoked potentials, but also in the suppression of segmental cervical motor evoked potentials with preservation of peripheral ones. The obtained data indicate the negative effect of hypoxia on the conducting function of the proximal part of the peripheral nervous system, which probably aggravates the process of motor recovery of patients with post anoxic encephalopathy.
Aim. Evaluation of the efficacy and safety of onasemnogen abeparvovec (OA) therapy in patients aged 1–34 months with spinal muscular atrophy (SMA) 5q with 2 or 3 copies of the SMN2 gene at preclinical and manifest stages of the disease development in the conditions of Children’s City Multidisciplinary Clinical Specialized Center for High Medical Technologies in Saint Petersburg.Materials and methods. According to the legislative acts of the Russian Federation and by decision of the Federal Council, children diagnosed with SMA without previous pathogenetic therapy received gene replacement therapy with OA in the conditions of the municipal children’s multidisciplinary clinical hospital in Saint Petersburg. Clinical efficacy was assessed initially and then every 6 months, lasting 24 months, using the motor assessment scales HINE-2 (qualitative neurological scale of infants), CHOP INTEND (for children unable to sit independently), and HFMSE (for patients capable of independent sitting). At the same time, the safety of OA was monitored by changes in clinical, laboratory and instrumental parameters.Results. 19 children aged 1–34 months with a body weight of less than 21 kg received OA therapy in the period from June 2022 to January 2025. The average dynamics on motor scales every 6 months in children with preclinical and manifest SMA was: CHOP INTEND – +16.1 points, HFMSE – +13.5 points; qualitative changes in neurological status were fixed on the HINE-2 scale. Adverse events (weakness/drowsiness, pyrexia, nausea, vomiting) developed 3–5 days after administration of the drug and were transient in nature. Immune-mediated liver hyperfermentemia of varying severity was detected in all patients: most often with an increase in alanine aminotransferase and aspartate aminotransferase values less than 2 times the norm – 15 (78.9 %) children in the range of 3–4 weeks; 2 (10.5 %) children had a second wave of hyperfermentemia at week 7–8. Severe hyperfermentemia with alanine aminotransferase and aspartate aminotransferase values exceeding two times but less than five times the upper limit of normal, and alanine aminotransferase and aspartate aminotransferase values exceeding five times the upper limit of normal, developed in 3 (15.7 %) of children, which required a change in the dose and duration of prednisone administration. Thrombocytopenia developed in patients at the preclinical and manifest stages of SMA in 4 (21.0 %) and 11 (57.8 %) cases, respectively. Platelet count normalization occurred in the period from 2 to 4 weeks. Troponin I was detected in 10 (52.6 %) children aged 2–8 weeks with less than a twofold increase in the upper limit of normal and decreased with prednisone maintenance doses. All deviations of laboratory parameters had different periods of normalization – from 10 days to 11 months. At the same time, there was no significant clinical deterioration requiring the transfer of patients to the intensive care unit.Conclusion. The use of OA for the treatment of SMA 5q with 2 or 3 copies of the SMN2 gene at preclinical and manifest stages of the disease in children aged 1 to 34 months demonstrates high efficacy and an acceptable safety profile. Obtaining optimal results is determined by the clinical manifestations at the time of gene replacement therapy and the comorbid background.
The co-occurrence of two genetic disorders in a single patient, so called double trouble phenomenon, is a rare clinical scenario that significantly complicates the diagnostic process. This is particularly challenging when both disorders affect the nervous system, leading to overlapping phenotypes. Congenital disorders of glycosylation, including the rare congenital 1i type caused by variants in the ALG2 gene, are characterized by psychomotor delay, microcephaly, seizures, hepatomegaly, and ophthalmological abnormalities. Joubert syndrome, associated with variants in the CPLANE1 gene, presents with brain malformations, severe psychomotor delay, oculomotor apraxia, and respiratory disturbances. In this study, we describe a patient with a rare combination of congenital disorders of glycosylation 1i type and Joubert syndrome type 17, caused by previously unreported variants in the ALG2 and CPLANE1 genes. This case highlights the diagnostic challenges and the need for a comprehensive approach in managing patients with multiple genetic disorders.
Background. Fatigue (athenia) is widely spread among patients with neurological disorders. It substantially reduces patients’ quality of life. Its clinical features and mechanisms of the development have not been studies sufficiently.Aim. To analyze clinical features of fatigue in patients with amyotrophic lateral sclerosis.Materials and methods. Forty two patients with amyotrophic lateral sclerosis were recruited to the study. Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI-20). The independent predictors of the severity of fatigue were calculated using linear regression analysis.Results. Fatigue was detected in 27 (64 %) patients. The most common type of fatigue was reduced activity, the least common – general fatigue. Severity of depression and motor neurological deficit were independent predictors of fatigue according to general MFI-20 score.Conclusion. Fatigue in amyotrophic lateral sclerosis is wide spread phenomenon. Its clinical features include both physical and mental components.
Background. Prolaptology is an area dedicated to the study and correction of pelvic organ prolapse, which remains an unsolved task of gynecology at the current stage of its development. Trampoline reflex – contraction of the pelvic floor muscles in response to an increase in intra-abdominal pressure in the “hammock mode/trampoline”. It is shown that the entire thickness of the pelvic floor muscles implements the trampoline reflex as a form of “fast” phasic reflex, and the background tone of the pelvic floor muscles is determined by “slow” tonic reflexes.Aim. To study the structural and functional organization of the trampoline reflex, to propose an experimental neurophysiological model of its objectification.Materials and methods. Data from open literature sources were used to build a theoretical neurophysiological model. An experimental neurophysiological model was built on the basis of a study of three healthy female volunteers over the age of 18 (average age is 30.00 ± 2.66 years). Registration of the trampoline reflex was carried out using an individual vaginal electrode (2nd channel of abduction) with unilateral stimulation of the diaphragmatic nerve and withdrawal of motor responses from the diaphragm (1st channel of abduction).Results. It is shown that the amplitude characteristics of the motor responses of the diaphragm of adult female subjects are significantly lower than those described earlier, and the motor response of the vaginal muscles during stimulation of the diaphragmatic nerve has a low amplitude, the principal possibility of its registration is associated with traumatic events from the bottom. The inversion of the motor response of the vaginal muscles is associated with the technical features of its registration.Conclusion. A neurophysiological model and a method for registering the reflex activity of the pelvic floor muscles are presented, which allows expanding the possibilities of diagnosing pelvic organ dysfunction from the position of impaired innervation of motor innervation and «imperfections» of the pelvic floor as an efferent link of the trampoline reflex.
Background. The main cause of morbidity and mortality in myasthenia gravis (MG) patients is respiratory failure that is based on subclinical respiratory disorders. Rehabilitation opportunities for such patients are limited by the frequent presence of a subjective feeling of fatigue that is important to distinguish from the main symptom of the disease – pathological muscle fatigability. This is determined by the need to achieve a balance between the obvious benefits of physical activity on the one hand and the rapid increase in fatigue and fatigability on the other and the peculiarities of the selection of physical exercises.Aim. To analyze the effectiveness of rehabilitation of MG patients with subclinical respiratory disturbances, to determine the level of fatigue in MG, to assess the effect of physical activity on fatigue.Materials and methods. The fatigue was studied in 53 MG patients using visual analog scale, “Well-being, activity, mood” questionnaire and fatigue assessment scale. Those who had no therapy enhancement within 6 months before the start as well as during the entire rehabilitation period were included in the study to determine the net effect of rehabilitation. The external respiration function was studied before and after the rehabilitation course. Before conducting the study a sample size planning method was used for independed and depended groups. Based on the results of the calculations a group of 22 patients with generalized MG without signs of respiratory disorders was formed to study the possibilities of rehabilitation.Results. According to the questionnaire a significant increase in the level (U, p = 0.002) and frequency of fatigue (χ2, p = 0.002), frequent poor health (χ2, p = 0.041 according to visual analog scale and χ2, p <0.0001 according to “Well-being, activity, mood” questionnaire), increased physical fatigue (U, p = 0.005) were showed. The negative effect of fatigue on well-being (rs = –0.78; p <0.05) and activity (rs = –0.73; p <0.05) was established. As a result of rehabilitation of MG patients with subclinical respiratory disorders a significant increase of vital capacity (W, p = 0.026) and inspiratory reserve volume (W, p = 0.044) were achieved.Good tolerance and absence of negative effects of physical exercise on general well-being (W, p = 0.495) on visual analog scale have been established. There was no deterioration on “Well-being, activity, mood” questionnaire: well-being (W, p = 0.467), activity (W, p = 0.396) and mood (W, p = 0.709). There was no increase in physical fatigue (W, p = 0.368) on fatigue assessment scale.Conclusion. Taking into account the pronounced effect of fatigue on the MG patient’s condition physical rehabilitation should be selected individually, preventing an increase in fatigue, muscle fatigability and weakness. Soft, mild or moderate intensity exercises are well tolerated and have no side effects.
Background. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a variant in the DMD gene, leading to severe disability and death at a young age. Today, in some variants in the DMD gene, etiopathogenetic therapy is possible to increase the patient’s life expectancy and improve his quality of life.Aim. To evaluate the dynamics of assess the dynamics of the ability to walk independently in patients with DMD caused by a nonsense variant in the DMD gene on the background of therapy with the drug ataluren.Materials and methods. The study included 9 patients with DMD caused by nonsense variants in the DMD gene. Of them, 3 patients were brothers and lost the ability to walk, 6 patients at the ambulatory stage of the disease received therapy with the drug ataluren according to the standard scheme. The six-minute walk test was chosen as the main parameter to assess the treatment efficacy in comparison with the baseline values before treatment.Results. According to the data of six-minute walk test during the observation period 5 patients taking ataluren during 18–36 months retained the ability to move independently. One patient who initially walked 12 m lost ambulation 6 months after starting ataluren therapy. Compared with 3 non-ambulatory brothers with DMD due to the DMD nonsense gene variant who did not receive ataluren, 3 younger brothers on ataluren therapy retained ambulation at an age when the older brothers had already become non-ambulatory.Conclusion. Pathogenetic therapy with the drug ataluren slows down the clinical course of DMD caused by a nonsense variant in the DMD gene with preservation of ambulatory capacity and is characterized by good tolerability.
Background. Spinal muscular atrophy 5q (SMA) is a severe genetic neuromuscular disorder, which is primarily manifested through musclar weakness. Previously, cognitive development in the natural course of SMA was considered normal. The introduction of etiopathogenetic therapy has altered the disease trajectory, led to new phenotypes, improved survival rates, and outlined the importance of studying the development of emotional, cognitive, and communicative domains, and adaptive behavior in SMA patients.Aim. To conduct a comprehensive assessment of emotional, cognitive, and adaptive domains, as well as speech development, in patients with genetically confirmed SMA, including cases, which were identified through newborn screening programs and were asymptomatic at the initiation of etiopathogenetic therapy, and to identify factors influencing neuropsychic development in SMA patients.Materials and methods. The study included 87 SMA patients receiving etiopathogenetic therapy, aged 0–12 years (median age at testing – 57.0 [37.0; 103.0] months). The Developmental Profile-3 (DP-3) instrument was used to assess neuropsychic development. Statistical analysis was performed using SPSS Statistics v.26.0 (IBM, USA).Results. Children who received therapy at the presymptomatic stage (6.9 % of the cohort) showed no deficits in any assessed developmental domains. These results significantly differed from those of SMA types 1, 2, and 3 in motor skills (padj <0.001) and adaptive behavior (padj ≤0.026). Patients with SMA types 1, 2, and 3 exhibited severe motor impairments (reduced motor skills in 93.0 %, 89.7 %, and 88.9 % of children, respectively) and adaptive deficits (impairments in ≥55 % of each group). SMA type 1 patients additionally demonstrated delays in social emotional (39.5 %), cognitive (30.2 %), and communicative (39.5 %) domains. Children with lower functional status (“lying”) had more pronounced delays in adaptive, social emotional, and cognitive domains (p ≤0.048). In SMA type 1, fewer SMN2 gene copies and earlier disease onset correlated with more severe deficits in emotional, cognitive, and adaptive domains, as well as in speech development (SMN2 copies: p ≤0.034; age of onset: p ≤0.012). SMA type 1 patients with dysphagia showed lower scores across all subscales except motor skills (p ≤0.015). Chronic respiratory insufficiency was associated with reduced scores in all five subscales: in SMA type 1, motor skills, adaptive, social emotional, and cognitive domains were affected (p ≤0.045); in SMA type 2, adaptive, social emotional, and cognitive domains were affected (p ≤0.018). Delayed therapy initiation correlated with lower motor and adaptive scores in SMA types 1 (p ≤0.012), 2 (p ≤0.002), and 3 (p ≤0.048), and with worse social emotional and cognitive outcomes in SMA type 2 (p = 0.001).Conclusion. SMA patients exhibit not only motor impairments but also adaptive and socialization deficits, as well as delays in communicative and cognitive development. A standardized approach to identifying these impairments should be developed, and developing tailored rehabilitation methods is important as well. Initiating etiopathogenetic therapy at the presymptomatic stage may prevent neuropsychiatric manifestations of SMA.
Immune checkpoint inhibitors have been used successfully over the last several years for treatment of many types of advanced cancer. Those agents cause uncontrolled activation of the immune system frequently resulting in immune-related adverse effects and exacerbation of pre-existing autoimmune diseases. In particular, immune checkpoint inhibitors can cause myasthenia which is usually characterized by an acute onset, rapid progression, and frequent development of myasthenic crisis requiring mechanical ventilation. Coexistence of myasthenia with myocarditis and myositis was shown to be an unfavorable prognostic factor. Steroids, intravenous immunoglobulins, and plasmapheresis are used for treatment of immune checkpoint inhibitor- associated myasthenia.
Hereditary spastic paraplegias represent a group of hereditary neurodegenerative disorders predominantly affecting corticospinal tracts which manifest with prominent spasticity and reduced power in the muscles of the lower limbs. According to clinical signs hereditary spastic paraplegias are divided into uncomplicated (classic) and complicated forms, according to the nature of inheritance – into autosomal dominant, autosomal recessive and X-linked. Mechanisms of the development of hereditary spastic paraplegias depend on the form and could be associated with misfolding of the proteins in endoplasmatic reticulum, mitochondrial dysfunction, changes in the cholesterol metabolism etc. Diagnosis is made after exclusion of other disorders of the central nervous system and could be confirmed by molecular genetic methods. Treatment of hereditary spastic paraplegias is symptomatic.
Hereditary spastic paraplegias represent a group of hereditary neurodegenerative disorders predominantly affecting corticospinal tracts which manifest with prominent spasticity and reduced power in the muscles of the lower limbs. According to clinical signs hereditary spastic paraplegias are divided into uncomplicated (classic) and complicated forms, according to the nature of inheritance – into autosomal dominant, autosomal recessive and X-linked. Mechanisms of the development of hereditary spastic paraplegias depend on the form and could be associated with misfolding of the proteins in endoplasmatic reticulum, mitochondrial dysfunction, changes in the cholesterol metabolism etc. Diagnosis is made after exclusion of other disorders of the central nervous system and could be confirmed by molecular genetic methods. Treatment of hereditary spastic paraplegias is symptomatic.
