Demyelination Of Nerve Fibers Research Articles

The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of flares via disease-modifying therapy. Primary drug therapies for acute flare include corticosteroids to limit inflammation and symptomatic management, depending on symptoms. Several different drugs have been recently approved for use in modifying the course of the disease, including a group of medications known as fumarates (e.g., dimethyl fumarate, diroximel fumarate, monomethyl fumarate) that have been shown to be efficacious and relatively safe. In the present investigation, we review available evidence focused on monomethyl fumarate, also known as Bafiertam®, along with bioequivalent fumarates for the long-term treatment of relapsing-remitting multiple sclerosis.

Ensemble Learning-based Multiple Sclerosis Detection Technique Using Magnetic Resonance Imaging

Multiple sclerosis (MS) is a complicated neurological disorder that leads to demyelination of nerve fibers in the central nervous system, causing severe symptoms and gradual impairment. Prompt and precise diagnosis of MS is essential for prompt intervention and individualized treatment planning. This research presents a new method for detecting MS: magnetic resonance imaging (MRI) data. Utilizing current progress in deep learning and ensemble learning methodologies, we use SWIN transformer and MobileNetV3-small for extracting features from MRI images. These features are then used for classification using CatBoost, XGBoost, and random forest algorithms. The suggested framework is tested and confirmed effective using the Kaggle MS database, which consists of various MRI images. The experimental findings show a remarkable average accuracy of 99.8% and a little loss of 0.07, highlighting the effectiveness of the suggested strategy in discriminating between aberrant and normal MRI pictures that indicate MS. This study enhances the field of medical image analysis by providing a precise and effective framework for automated diagnosis of MS. This framework has the potential to enhance diagnostic efficiency and improve patient outcomes. Combining deep learning feature extraction with ensemble classifiers offers a robust and easily understandable approach for diagnosing MS and has the potential to be used in clinical settings. Future research should prioritize validating the suggested technique on more extensive datasets and incorporating it into clinical practice to enhance early identification of MS and provide individualized patient treatment.

Relationship Between Trunk and Lower Extremity Muscles and Balance in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease that causes demyelination of nerve fibers. This neurological process causes physical and mental changes in and to the motor, sensory, and cognitive systems. This study aims to determine the relationship between balance and muscle strength in people with multiple sclerosis. This study included 36 MS patients’ ⩾18 years old who were treated and followed up according to routine clinical practice at a university hospital in Türkiye, which were observational, non-invasive, and a control group of 32 patients whose relatives were voluntarily evaluated without any neurological problems. Muscle strength was measured manually. In balance analysis, computerized balance analysis system was used. The mean age of the MS group was 46.14 (SD±7.14) and the mean age of the healthy group (HG) was 42.25 (SD±10.81). While muscles of abdominal, hamstring, hip flexor and extensor, tibialis anterior and tibialis posterior muscle strength were found to be positively significant with balance in the MS group, P0.05). This study revealed significant correlations between balance and strength parameters of trunk and lower extremity muscles. Our study suggests that rehabilitation protocols for MS patients should include a critical strength training program, especially for trunk and lower extremity muscles.

Immunohistochemical Study of Macrophages of Sciatic Rat Nerve after Damage and Subperineural Injection of Mesenchymal Stem Cells

The dynamics of the processes of Wallerian degeneration in the Wistar-Kyoto rat sciatic nerve after injury (ligation, 40 s) was studied.The density of Iba-1+ macrophages and the state of myelin fibers stained with Luxol strong blue in the distal segment of the nerve at different times after injury were studied. Parts of rats were subperineurally transplanted with MSCs from the bone marrow of Wistar-Kyoto rats. It was shown that the highest distribution density of macrophages in the distal segment of the nerve was observed 7 days after surgery. The use of cell therapy leads to a decrease in the number of macrophages during this period and to a delay in the demyelination of damaged nerve fibers. Sixty days after the operation, the macrophage population density and the number of remyelinated regenerating nerve fibers of the distal nerve segment did not differ in control (ligature) and experimental (ligature and MSC injection) animals. The molecular mechanisms of the noted changes in the early stages after injury require further research.

PATHOGENESIS OF AUTONOMIC AND PERIPHERAL NEUROPATHY IN PATIENTS WITH PSORIASIS

There is enough data confirming the common mechanisms of damage to the nervous system and skin in psoriasis. Cardiac autonomic denervation is a mechanism of cardiovascular pathology in psoriasis. Thus, a simultaneous disturbance of sympathetic and parasympathetic impact on vascular tone and heart rhythm has been established. When performing an active orthotest in trial subjects, heart rate centralization and decreased autonomous circuit activity were found. In psoriasis, vegetative-vascular dystonia develops due to metabolic disorders that occur in diabetes mellitus. Inflammatory cytokines Th-1, adhesion molecules, and angiogenic factors are involved in pathological processes in obesity, diabetes, metabolic syndrome, and thrombotic complications. Microangiopathy, which develops in psoriasis, reduces the response of blood vessels to autonomic innervation. Such negative influences eventually lead to a persistent alteration of the autonomic nervous control. The authors resent the results of a few studies on the peripheral nervous system in patients with psoriasis. There is evidence of a symmetrical alteration of vibration, tactile, pain and temperature sensitivity in the distal regions of all four limbs. There are some histological studies of the sural nerve in patients with psoriasis, which indicate demyelination of nerve fibers. In this regard, the study of neuropathy pathogenesis in psoriasis is necessary to improve the disease course and the effectiveness of psoriasis therapy.
 Assessment of psoriatic lesion severity and timely detection of cardiac denervation will reduce the risk of fatal cardiovascular complications. Instrumental diagnostics of the peripheral nervous system will make it possible to differentiate damage to muscle and nerve fibers in psoriasis.

Investigation of the pathogenesis, clinical course, and early and late consequences of the zone of perifocal edema of glial brain tumors with its surgical and drug correction

Introduction and Aim: Perifocal edema are the cause of the severity of patients, increasing intracranial pressure and dislocation syndrome. The objective of this study is to plan an adequate approach to the area of perifocal edema in the treatment of patients with glial brain tumors by studying the pathogenesis and consequences.
 
 Methods: 720 patients with glial tumors with varying degrees of malignancy and a zone of perifocal edema were operated and of these, 281 patients with GRADE I-IV astrocytoma, 147 patients with GRADE I-III oligodendroglioma, 115 patients with GRADE I-III ependymoma, and 177 patients with GRADE IV glioblastoma. The zone of perifocal edema was assessed by a point system from 1–5 points.
 
 Results: The glial tumor was significantly more common in the age group of 45-59 years (44.9 ± 2.1 cases per 100 patients). In the zone of perifocal edema at a distance from the tumor up to 1.5-2.0 cm, there was a site of apoptosis, demyelination, and destruction of nerve fibers.
 
 Conclusion: The surgical approach proposed by us with the removal of the apoptosis zone and the zone of perifocal inflammation is the key to the successful recovery of patients, without or with minimal postoperative complications.

Natural Killer Cells Disrupt Nerve Fibers by Granzyme H in Atheriosclerotic Cerebral Small Vessel Disease.

Natural killer (NK) cells are enriched in the central nervous system in aging-related atheriosclerotic cerebral small vessel disease (aCSVD), but their roles and underlying mechanism remain to be elucidated. To identify potential cytotoxic molecules released by NK cells in aCSVD lesions, proteomic analysis of cerebrospinal fluid (CSF), plasma, and peripheral NK cells from patients with aCSVD were performed. We found that integrin β2 (ITGB2), cathepsin D (CTSD), and granzyme H (GZMH) were highly expressed in NK cells. ITGB2 interacted with intercellular adhesion molecule 1 in vascular endothelial cells. As assessed by immunofluorescence and scanning electron microscopy of the blood-brain barrier model, transwell membranes covered with primary human brain microvascular endothelial cells and astrocytes, we demonstrated that the CTSD-mediated degradation of collagen in the blood-brain barrier depended on the cytotoxicity of NK cells in aCSVD. With the immunostaining in vitro and in vivo, GZMH disruption of demyelinated nerve fibers was reversed by cotreatment with the inhibitor 3,4-DCIC during white matter hyperintensity (WMH) in aCSVD. Our results indicate that NK cells contribute to CTSD-induced damage to the blood-brain barrier and GZMH-induced disruption of nerve fibers during WMH in aCSVD.

Gait Disorders and Magnetic Resonance Imaging Characteristics in Older Adults with Cerebral Small Vessel Disease.

This study aims to explore the features of gait disorders with cerebral small vessel disease (CSVD), and results from magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were analyzed. The 139 patients with CSVD were divided into two groups by the Tinetti scale scores: the gait disorder (GD) group with a score <24 (63 patients) and the normal gait (GN) group with a score ≥24 (76 patients). A series of scales and 3.0T MRI with DTI were used to analyze the correlation between the abnormal gaits and imaging findings. The differences in the Barthel Index, Unified Parkinson's Disease Rating Scale part III, and Montreal Cognitive Assessment (MoCA) scores between the two groups were significant (p < 0.05), and there were significant correlations between MoCA and total gait scores (r = 0.201, p = 0.002). The GD group had a more degraded gait score, widened gait base, and degraded gait length than the GN group (p < 0.05). There were significant differences between the two groups (p < 0.05) in white matter (WM) hyperintensities (WMH) of the Fazekas scale grade 2-3 and lacunes. The GD group had a greater total MRI burden than the GN group (p < 0.05). In DTI parameters, the GD group had lower fractional anisotropy (FA) and higher mean diffusion (MD) values in WM tracts in many areas around the ventricles (family-wise error corrected, p < 0.05). Significant correlations were observed between FA and the total gait score (r = 0.467, p < 0.01), and also between MD and total gait score (r = -0.422, p < 0.01). Patients with CSVD with gait disorders had more WMH of Fazekas scale grade 2-3, lacunes, and total MRI burden than the GN patients, and those with gait disorders may suffer from demyelination of nerve fibers and damage to the fibers' microstructures.

In Vivo Assessment of the Ameliorative Impact of Some Medicinal Plant Extracts on Lipopolysaccharide-Induced Multiple Sclerosis in Wistar Rats.

Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants (N. hindustana, V. negundo, and A. albiflora) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana, V. negundo, and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana, V. negundo, and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis.

Analgesic and neuroprotective effects of Baimai Ointment on diabetic peripheral neuropathy

Ethnopharmacology relevanceBaimai (BM) ointment, a traditional Tibetan medicine, has been widely used to treat “white vein” disease, paralysis, hemiplegia and claudication caused by trauma, because of its great effects on muscle stretching and collateral activation. As one of the most terrible complications in diabetes patients, diabetes peripheral neuropathy (DPN) is mainly manifested as abnormal pain or numbness in extremities. However, whether BM ointment is a potential drug for DPN treatment is unclear. Aims of the studyThe aim of this study was to investigate the therapeutic effects of BM on DPN in a high-fat diet/low-dose of streptozotocin induced type 2 diabetes rat model and explore underlying mechanisms. MethodsThe chemical components of BM were determined by high performance liquid chromatography (HPLC), and the possible targets and related pathways candidates involved in the effects of BM on DPN were predicted using network pharmacology methods. Next, the effects of different doses (1.5, 3.0 and 6.0 g/kg) of BM on physiological changes, pain behaviors, motor nerve conduction velocity (MNCV) in DPN rats were assessed and compared with placebo- and mecobalamine (Meco)-treated DPN controls. Then, the effects of BM on the expression of pain associated genes as well as the phosphorylation of PI3K/AKT and MAPKs pathways in DRG of DPN rats were examined. ResultsThrough HPLC analysis, curcumin was identified as one of the primary contents of BM. The information from network pharmacology indicated a series of target candidates for BM including IL6, IL10, TNF, CCL2, CXCL12, EGF, VEGFA, BDNF, TGFβ1 and TNF, as well as PI3K-AKT and MAPK signaling pathways. Topical treatment of BM significantly improved the hypersensitivity of mechanical and thermal pain, MNCV and the morphological changes and demyelination of sciatic nerve fibers, without affecting the body weight, serum metabolism or blood glucose. The up-regulated levels of neuropeptides Cgrp, Sst, Sp and chemokines Ccl2 and Ccl3 along with the abnormal expression of p-P38, p-ERK and p-AKT in the DRG of DPN rats were alleviated by BM application. ConclusionBM ointment has great activities in relieving pain hypersensitivity, neuroprotecting peripheral nerves damage caused by DPN, which may be related to the inhibition of related neuropeptide (Cgrp, Sst, Sp) and chemokine (Ccl2, Ccl3) expression and the regulation of PI3K/AKT and MAPKs signaling pathways in DRG.

Abstract- Poster

Introduction:Multiple sclerosis is an autoimmune disorder that affects the central nervous system by causing demyelination of nerve fibers. Both Demyelination, nerve damage and stress of relapsing symptoms can cause Depression and related disorders. Even the medications used for MS can lead to neuropsychiatric manifestations.Case study:A 24 year old female came to OPD with complaints of low mood, anhedonia, easy fatiguability, death wishes and crying spells since 1 month. History revealed diagnosis of Multiple sclerosis when she experienced similar mood symptoms and frequent panic attacks for which she was treated with SSRIs for 6 months. Patient has been in remission until 2 months ago when she developed left lower limb weakness and relapse, following which depressive symptoms were reported and was started on SSRIs with significant improvement.Conclusion:Multiple sclerosis in itself based on location of the lesions can trigger Depression and at the same time the long-standing nature of the disease and relapses can trigger Depression as they act as stressors. So, there is a need for us to evaluate and monitor the signs and symptoms of Depression and anxiety along with MS relapses as studies have association.

Spinal cord injury

A spinal cord injury (SCI) is damage to any part of the spinal cord or nerves extending from the spinal cord that often results in permanent changes in motor and/or sensory abilities and other body functions below the point of the injury. The physical impairments from SCI vary as a function of the level and completeness of the injury. Nearly every aspect of a person's life physical health, work, personal relationships, and recreation may be affected following SCI. Adjustment involves learning new adaptive behaviors and attitudinal change, so psychologists play a crucial role in assisting the rehabilitation process. This self-directed learning module highlights basic management and approaches to intervention both established and experimental. The revised American Spinal Injury As sociation classification of spinal cord injury (SCI) further defines the examination and classification guidelines. The incidence of traumatic SCI remains at approximately 10,000 cases per year, with 32 years the average age at injury. Initial management includes establishment of oxygenation, circulation (mean blood pressure >85mmHg), radiographic evaluations for spine instability, intravenous methylprednisolone, and establishment of spinal alignment. Prevention measures for medical complications include pressure relief for skin, thromboembolism prophylaxis, prevention of gastric ulcers, Foley catheter drainage to prevent urine retention, and bowel care to prevent colonic impaction. Nontraumatic SCI from spinal stenosis, neoplastic compression, abscess, or multiple sclerosis becomes more common with aging. Experimental treatments for SCI include antibodies to block axonal growth inhibitors, gangliosides to augment neurite growth, 4-aminopyridine to enhance axonal conduction through demyelinated nerve fibers, and fetal tissue to fill voids in cystic spinal cord cavities. Early comprehensive rehabilitation at a SCI center prevents complications and enhances functional gains.

PECULIARITIES OF THE COURSE, DIAGNOSIS, AND TREATMENT OF MULTIPLE SCLEROSIS

Introduction. Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system, which is characterized by demyelination and degeneration of nerve fibers and has a polymorphic clinical picture and a tendency to an unfavourable course [1]. The disease usually affects young and working-age people, leading to early disability and poor quality of life, which makes it a socially significant problem of our time [2]. The main objective was to increase the efficiency of diagnosis and treatment of patients with multiple sclerosis based on a comprehensive analysis of clinical-neurological, psychodiagnostic, and neuroimaging features of the onset and course of the disease. Materials and Methods: Clinical and neurological examination of patients using the Functional System Score (FSS) and Expanded Disability Status Scale (EDSS); cognitive functions examination using the Mini-Mental State Examination (MMSE), the clock-drawing test, the five-word test; brain magnetic resonance imaging; the 36-Item Short Form Health Survey (SF-36). According to statistics, there are about 3 million patients with multiple sclerosis worldwide. In Ukraine, about 20,000 people have multiple sclerosis. Currently, a hypothesis has been made about multiple sclerosis as a multifactorial disease that is, to a great extent, attributable to genetic predisposition (i. e., features of the immune reaction) and the influence of external factors [1]. Multiple sclerosis mainly affects young and mature people – 12 to 55 years old. Although multiple sclerosis can sometimes make its debut in puberty, however, the frequency of the disease gradually increases with age up to the middle of the third decade of life, with a subsequent decrease up to the age of 50–60 [3]. Recently, a trend toward the rejuvenation of multiple sclerosis has been observed. About 3% of all patients with multiple sclerosis are children under 16. Multiple sclerosis debuting at a later age is not sufficiently studied and is rarely diagnosed, although in about 20% of patients, the first signs of this pathology appear after age 40 [4, 11].

Diabetic ulcer with diabetic neuropathy: a rare clinical image.

A diabetic ulcer is a non-healing ulcer seen in people with uncontrolled blood sugar. High blood sugar causes the formation of sorbitol from sugar, which causes demyelination of large nerve fibers. Here we reported a case of a 62-year-old male who came to the medicine outpatient department with the complaint of a large ulcer over the anterior aspect of the right leg. In diabetic patients, there is an altered immune system and poor blood flow. On physical examination, there is loss of epithelium with granulation tissue formation and decreased sensation, doctors suggested a diagnosis of diabetic ulcer with diabetic neuropathy. On lab investigation, the patient was diagnosed with Type II diabetes with an uncontrolled blood sugar of chronic duration.

Multiple Sclerosis, Chlamydia and Gut Disbiosis

I believe that multiple sclerosis progression could be stopped through antibiotics, dewormers, beta glucans and garlic extract and, by far the most difficult, changing the quality of the water ingested, or used for washing salads, in addition to increasing the consumption of probiotics. I believe that MS sclerosis is due to the unfortunate encounter of 3 diseases: intestinal dysbiosis, chlamydia infections and orthopedic problems. However, how would these three diseases cause demyelination of nerve fibers?

The effect of age on self-rated skin pain in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a recalcitrant chronic inflammatory skin disease characterized by recurrent and painful nodules that negatively affect health-related quality of life. Pain is the most disabling symptom of HS, but data on HS pain remain limited. We previously observed a dissociation between pain and number of HS lesions with regards to increasing age. To further explore this observation, we investigated the relationship between experienced HS pain and age, adjusting for other relevant factors that might affect pain assessment. We conducted a retrospective cohort study (n = 342) using data from the Registry for Hidradenitis Suppurativa database. Multiple linear regression analysis was performed for self-evaluated pain (measured on a 0-10 numerical rating scale [NRS]) as an outcome with age and adjusted for the effects of sex, BMI, smoking status, lesion count and percentage of lifetime spent with HS symptoms. The multiple linear regression showed that age was associated with a decreased pain level of 0.31 NRS points/year (95%CI: -0.062; -0.0088; p = 0.044) and number of nodules was associated with an increased pain level of 0.081 NRS points/nodule (95%CI: 0.00077; 0.16; p = 0.048). Percentage of lifetime spent with HS symptoms was not found to significantly affect pain levels. This study supports our hypothesis that older HS patients report decreased levels of pain, independent of disease severity, which may be due to factors such as demyelination of nerve fibres, reduced painful physical activity, improved coping, or associated co-morbidities that distract from HS-related pain.

Multiple sclerosis as one of the causes of disability at a young age

Multiple sclerosis is one of the most severe degenerative diseases of the central nervous system and is a variant of autoimmune pathology, in which demyelination and degeneration of nerve fibers occurs, against which there is a violation of their conduction. Its development occurs gradually and has a pronounced staging of the pathological process. The disease occurs as a result of the combined interaction of external factors (viruses, infection, intoxication, dietary characteristics, exposure to stressful situations, poor ecology) and hereditary predisposition. In the world, there are about 3 million patients suffering from various forms of multiple sclerosis. As a result of this pathological process, the central and peripheral nervous system is damaged mainly in young people of working age, which leads to their early disability, limitation of life opportunities, and gives reason to consider this disease a socially significant issue of our time.

Показники стимуляційної електронейроміографії в пацієнтів iз первинним гіпотиреозом

Мета дослідження — виявити електронейроміографічні особливості ураження периферичної нервової системи в пацієнтів iз первинним гіпотиреозом на фоні автоімунного тиреоїдиту (АІТ) та післяопераційного гіпотиреозу шляхом проведення стимуляційної електрoнейроміографії (ЕНМГ). Матеріали та методи. Обстежено 56 хворих на гіпотиреоз на фоні АІТ та 19 пацієнтів iз післяопераційним гіпотиреозом. Контрольну групу становили 20 практично здорових осіб. П’ятдесят сім (76 %) пацієнтів отримували замісну терапію синтетичними похідними L-тироксину, у 18 (24 %) хворих був субклінічний гіпотиреоз. Проведено комплексне клініко-неврологічне та електрофізіологічне обстеження хворих, що включало ЕНМГ-тестування моторних (малогомілкові, великогомілкові, серединні) та сенсорних (малогомілкові, литкові) нервів. При дослідженні моторних нервів оцiнювали наступні показники: амплітуду та тривалість М-відповіді, площу М-відповіді на стимуляцію нерву в дистальній та проксимальній точках, термінальну латентність, резидуальну латентність, швидкість проведення збудження (ШПЗ), при вивченні сенсорних нервів — амплітуду потенціалу дії та ШПЗ. Результати. За АІТ спостерігалось ураження сенсорних нервів нижніх кінцівок (поверхневi малогомілковi та литковi) за змішаним типом. Аксонопатія проявлялась у зменшенні амплітуди потенціалу дії поверхневого малогомілкового нерва на 32,7 % (p &lt; 0,05) та литкового на 27,5 % (p &lt; 0,05) порівняно з контрольною групою, також відмічали зниження ШПЗ малогомілковими нервами на 21,9 % (p &lt; 0,05), що свідчить про пошкодження мієлінової оболонки. У пацієнтів iз післяопераційним гіпотиреозом спостерігалися переважно ознаки аксонопатії, про що свідчило зменшення амплітуди потенціалу дії поверхневого малогомілкового нерва на 27,9 % (p &lt; 0,05). При дослідженні функції рухових волокон периферичних нервів (сере­динний, малогомілковий та великогомілковий) виявлено, що ураження моторних волокон мало демієлінізуючий характер у 78,8 % випадків, у решти хворих (22,2 %) полінейропатія була змішаною (з ознаками ураження мієлінової оболонки та аксонів). Пошкодження ліктьових та великогомілкових нервів було облігатним, у той же час ознаки ураження серединного нерва спостерігалися в 72,8 % випадків. Про демієлінізацію швидкопровідних волокон малогомілкових та великогомілкових нервів свідчило подовження резидуальної латентності на 31,7 % (p &lt; 0,05) та 31,6 % відповідно (p &lt; 0,05), зниження ШПЗ при тестуванні малогомілкових нервів на 21,5 % (p &lt; 0,05) та на 19,4 % — при дослiдженні великогомілкових нервів. З боку серединних нервів відмічалося незначне зниження амплітуди дистальної М-відповіді, на ураження мієлінової оболонки вказувало статистично вірогідне підвищення резидуальної латентності та незначне зниження ШПЗ. У 22,2 % хворих з АІТ відмічалися ознаки поєднаного ураження мієлінової оболонки та аксонального пошкодження, коли крім зниження ШПЗ руховими волокнами великогомілкового та малогомілкового нервів на 21,7 та 21,4 % та деякого підвищення резидуальної латентності спостерігалося вірогідне зниження амплітуди М-відповіді на 15,6 та 14,8 % відповідно. У пацієнтів iз післяопераційним гіпотиреозом відмічалися лише ознаки мієлінопатії. Висновки. ЕНМГ дозволила виявити демієлінізуючий та змішаний характер ураження моторних волокон та аксональний характер ураження сенсорних периферичних нервів, причому більш виражені зміни спостерігалися при АІТ, ніж при полінейропатії на фоні післяопераційного гіпотиреозу.

Ultrastructural changes in the spinal cord of rats with experimental allergic encephalomyelitis under the influence of human umbilical cord-derived multipotent mesenchymal stromal cells cryopreserved according to different protocols

The transplantation of multipotent mesenchymal stromal cells (MMSCs) is considered to be a possible therapy of multiple sclerosis. For the clinical application of human umbilical cord-derived MMSCs (UC-MMSCs) it is necessary to develop a method of their cryopreservation taking into account the type of cryoprotective media and to investigate the possibility of using these cells for therapeutic purposes in vivo. The purpose of the study was to investigate the effect of UC-MMSCs, cryopreserved in solutions of different composition, on the processes of demyelination and remyelination of the spinal cord of rats with experimental allergic encephalomyelitis (EAE) as a model of multiple sclerosis. Materials and methods. The EAE was modeled by subcutaneous administration of homogenized spinal cord of adult rats with complete Freund's adjuvant. On the 18th day rats with moderate relapsing-remitting form of EAE were suboccipitally injected 1•106 UC-MMSCs, cryopreserved in cryoprotective media containing dimethyl sulfoxide (DMSO), fetal bovine serum (FBS), ethylene glycol, trehalose and sucrose at different composition. On the 35th and 60th days, the studies of ultrastructural changes of the lumbar spinal cord (L3-L5) were performed, assessing the degree of demyelination of nerve fibers by the ratio of myelin sheath (MS) thickness to the diameter of the axis cylinder (AC) of axons. Results. In rats with moderate EAE from the 35th to the 60th day after the modelling of the disorder, destructive changes and signs of demyelination in the spinal cord increased; the MS/AC index corresponded to the average degree of axon demyelination. Suboccipitally administered cryopreserved UC-MMSCs to EAE rats, depending on the used cryopreservation solution, slowed or stopped the demyelination, decreased the MS/AC index to a low degree of axonal demyelination. Reducing the concentration of DMSO in the cryopreservation medium from 10 % to 4 % and adding 6 % trehalose provided a better effectiveness of UC-MMSCs in decreasing the degree of demyelination in EAE. At the same time, the standard solution (10 % DMSO, 90 % FBS) provided these effect, but to a lesser extent. The use of a multicomponent cryopreservation medium containing 15 % ethylene glycol, 3 % DMSO, 10 % sucrose, 12 % trehalose and 60 % FBS did not achieve the goal of maintaining the effects of UC-MMSCs to reduce the degree of demyelination in EAE. Conclusions. To maintain the therapeutic properties of UC-MMSCs, it is advisable to add a reduced concentration of DMSO (4 %) and 6 % trehalose to the cryopreservation medium, supplemented with 90 % fetal bovine serum.

Analysis of a Chinese pedigree with autosomal dominant Charcot-Marie-Tooth disease type 2A2A

To explore the genetic basis of a pedigree affected with peroneal muscular atrophy. Neuroelectrophysiological examination and whole exome sequencing were carried out for the proband, a six-year-and-ten-month-old boy. Suspected variant was verified in his family members through Sanger sequencing. Bioinformatic analysis was carried to predict the conservation of amino acid sequence and impact of the variant on the protein structure and function. Electrophysiological examination showed demyelination and axonal changes of motor and sensory nerve fibers. A heterozygous missense c.1066A>G (p. Thr356Ala) variant was found in exon 11 of the MFN2 gene in the proband and his mother, but not in his sister and father. Bioinformatic analysis using PolyPhen-2 and Mutation Taster software predicted the variant to be pathogenic, and that the sequence of variation site was highly conserved among various species. Based no the American College of Medical Genetics and Genomics standards and guidelines, the c.1066A>G (p. Thr356Ala) variant of MFN2 gene was predicted to be likely pathogenic (PS1+ PM2+ PP3+ PP4). The heterozygous missense c.1066A>G (p.Thr356Ala) variant of the MFN2 gene probably underlay the disease in the proband, and the results have enabled genetic counseling and prenatal diagnosis for this family.