Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc. (multiplex analysis) were studied. In the present work, ultrastructural and immunohistochemical apoptotic signs were found in neurons and oligodendrocytes in the temporal lobe of DRE patients. Levels of proinflammatory cytokines that play a role in apoptosis (TNF-α, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-α is increased and IL-2 is reduced. Oligodendroglial apoptosis has been shown to play an important role in DRE pathogenesis and to explain demyelination. Thus, a comprehensive analysis of revealed changes in the blood and brain in DRE patients showed the neuroinflammation in the epileptic focus, which was combined with the development of apoptosis of glial cells and neurons. This creates conditions for the development of drug resistance and the epilepsy progression.
The European Commission of the International League Against Epilepsy (ILAE) has identified glial mechanisms of seizures and epileptogenesis as top research priorities. The aim of our study was to conduct a comparative analysis of the expression levels of cytoskeletal proteins (glial fibrillar acidic protein (GFAP) and vimentin), protective protein S100, and proapoptotic caspase-3 protein in patients with drug-resistant epilepsy (DRE) associated with focal cortical dysplasia (FCD). We aimed to investigate how the expression levels of these proteins depend on age (both in children and adults), gender, and disease duration, using immunohistochemistry. Nonparametric statistical methods were employed for data analysis. In the epileptic focus area of the cortex and white matter in patients with FCD-associated temporal lobe DRE, a higher level of expression of these proteins was observed. Age and gender differences were found for vimentin and S100. In the early stages of disease development, there was a compensatory sequential increase in the expression of cytoskeletal and protective proteins. In patients with DRE, depending on the disease duration, patterns of development of neurodegeneration were noted, which is accompanied by apoptosis of gliocytes. These results provide insights into epilepsy mechanisms and may contribute to improving diagnostic and treatment approaches.
1 January 2017 in Epilepsy and paroxysmal conditions
Objective. To identify predictive factors of favourable outcomes in children with drug resistant epilepsy (DRE) associated with structural brain changes, who received surgical treatment. Methods. We performed a retrospective analysis of surgical treatment in 239 children with drug resistant epilepsy treated at the Pediatric Neurosurgery Department of the A. L. Polenov Russian Neurosurgical Institute from 2004 to 2014. The age of the patients varied between 2 and 18 years. The follow-up time ranged from 1 year to 10 years (on average 4.3 years). Results. According to magnetic resonance imaging (MRI), 223 (93.3%) patients had different structural brain changes. Among the patients, 47 (21.1%) had cerebral cicatrix, gliosis, cysts and atrophic changes, 33 (14.8%) had malformations of the cortical development, 43 (19.3%) had benign brain tumors, 47 (21.1%) had vascular malformations, 21 (9.4%) had arachnoid cysts, 12 (5.4%) had hippocampal sclerosis, 11 (4.9%) had phacomatosis, 5 (2.2%) had Rasmussen’s encephalitis, and 4 (1.8%) had hypothalamic hamartoma. Positron emission tomography revealed the areas of gray matter hypometabolism in the brain, which correspond to the areas of a metabolic deficiency around the epileptic focus. Favorable long-term outcomes of epilepsy surgery (class I according to Engel scale) were registered in 67.6% of the cases. The most favorable results (class I according to Engel scale) were achieved after lesionectomy (81.9%), temporal resections (78.4%), and hemispherectomy (72.7%). Conclusions. The most important predictive factors of favorable outcomes after epilepsy surgery are as follows: detection of epileptogenic morphological changes of the brain, completeness of resection of an epileptic and epileptogenic areas, and absense of seizures in the early postoperative period.
The chapter discusses modern and promising approaches to the use of CSF shunting operations in children. CSF shunting operations remain the only effective method for correcting persistent CSF circulation disorders in CSF resorption disorders with the development of intracranial hypertension and hydrocephalus. The chapter is devoted to general ideas about CSF dynamics and biomechanical properties of the craniospinal system that affect CSF dynamics, and gives a pathogenetic assessment of CSF dynamics in the development of intracranial hypertension and hydrocephalus. Aspects of genetics and genomics of anomalies in hydrocephalus are touched upon. Pathological changes in the brain around old ventricular shunts are described. The authors consider the types of CSF shunting operations for hydrocephalus in children. Possible complications of CSF shunting operations are analyzed with the algorithm for their correction and management tactics for this group of patients.
1 July 2021 in Journal of Evolutionary Biochemistry and Physiology
Chronic disorders of consciousness (DOC) leads to the development of skeletal muscles dysfunction (weakness, pareses)—critical illness polyneuropathy and myopathy. It is of interest to study the mechanisms underlying the development of this pathology and to assess the rehabilitation potential of DOC patients. Using positron emission tomography and computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG), as well as pathomorphological and immunohistochemical methods, we obtained data on structural and metabolic changes in the skeletal muscles of the upper extremities in 22 DOC patients. The study showed that structural changes in skeletal muscles have a nonspecific degenerative-atrophic nature and manifest severely on the side of paresis. In DOC patients, metabolic disorders of the shoulder girdle muscles, as revealed by a decrease in the level of 18F-FDG metabolism, developed symmetrically, regardless of muscle tone and deep reflexes levels. Along with degenerative changes, including damage to the contractile elements of the sarcomeres, the loss of desmin and dystrophin, and a decrease in the level of 18F-FDH metabolism, skeletal muscles of DOC patients revealed the signs of adaptive structural and functional rearrangements, such as a slow-to-fast transformation of the muscle fiber phenotype and activation of the autophagic pathway.
Method: A total of 33 patients with glial brain tumors of supratentorial localization (Grade II - 8, Grade III - 11, Grade IV - 15). All patients underwent intraoperative fluorescence diagnostics with chlorine E6 of the 2nd generation (1 mg / kg), and the contrast was assessed in preoperative MRI images in T1 mode and PET with methionine. The contrast assessment on MRI was carried