[Morphological characteristics of the brain nervous tissue during aging]. / Morfologicheskaya kharakteristika nervnoi tkani golovnogo mozga pri starenii.

OBJECTIVE: Identification of morphological manifestations and evaluation of morphometric parameters of the nervous tissue in various structures of the human brain during aging. MATERIAL AND METHODS: Autopsy material was obtained from patients whose causes of death were not associated with neurological diseases. Three age groups were studied: young (35-45 years old) (n=10); eldery (75-89 years old) (n=20); centenarians (over 90 years old) (n=10). Quantitative analysis of large neurons in the compact part of the substantia nigra, basal ganglia, layer V of the cortex, and the pyramidal layer of the hippocampus was carried out. In addition, the brain mass, the thickness of the cortex of the precentral gyrus were measured, the glial index was calculated, and the morphological signs of age-related involution of the brain tissue and intracerebral vessels were assessed. RESULTS: In senile and centenarians, compared with young people, there was a progressive reduction in large neurons of layer V of the cortex, basal ganglia, the pyramidal layer of the hippocampus and substantia nigra, a decrease in brain mass and thickness of the cortex of the precentral gyrus, as well as an increase in the glial index. Changes in blood vessels characteristic of aging are described. Also, during aging, signs characteristic of neurodegeneration were found. CONCLUSION: The results of the study confirm that such brain structures as the cortex of the precentral gyrus, the hippocampus, the basal ganglia, and the substantia nigra lose large neurons with age, followed by the development of gliosis. The identified morphological changes characteristic of aging are phenomenologically similar to a certain set of morphological changes in neurodegenerative diseases of late age.

[Small focal cerebral ischemic changes caused by hypertension and tandem atherostenosis of the cerebral arteries]. / Melkoochagovye ishemicheskie izmeneniya golovnogo mozga, obuslovlennye arterial'noi gipertoniei i tandemnym aterostenozom tserebral'nykh arterii.

Postmortem studies are of great importance in evaluating the effectiveness of clinical, diagnostic, therapeutic, and preventive measures aimed at combating a social disease, such as dyscirculatory encephalopathy, the leading causes of which are hypertension and atherosclerosis. The complexity of these studies is largely determined by a variety of brain changes with the frequent concurrence of hypertension and severe cerebral atherosclerosis and, at the same time, the similarity of some changes, for example, the localization and size of hypertensive and atherosclerotic lacunar infarcts. The paper describes a case of dyscirculatory encephalopathy with multiple small focal cerebral ischemic changes caused by both hypertension and athero-stenosis of several arteries in both the brain carotid systems and the vertebrobasilar system, namely tandem stenoses. It has been established that small infarcts in tandem stenosis can result from adaptive processes in the intracranial arteries. These infarcts have some features of localization, such as the areas of adjacent blood supply to the cerebral hemispheres and cerebellum, as well as the deep regions of the brainstem. It is shown that arterial pathological changes in the ischemic zones permit one to make a differential diagnosis of hypertensive lacunar infarcts and the same infarcts arising in tandem stenoses. In addition, among the typological signs of hypertensive lacunar infarcts, there are enlarged perivascular spaces in the peri-infarct region and ischemic destruction of myelin in the periventricular regions of the brain.

[Current state of cerebral microangiopathy in hypertension]. / Sovremennoe sostoyanie problemy tserebral'noi mikroangiopatii pri arterial'noi gipertenzii.

Hypertension is the main cause and the most important risk factor for both acute cerebrovascular accident and chronic progressive cerebrovascular insufficiency that is accompanied by severe neurological and mental disorders even to the extent of developing dementia. They are based on hypertension-induced pathology of the intracerebral arteries and cerebral microvasculature - cerebral microangiopathy that leads to small deep (lacunar) infarcts (SDIs) and diffuse cerebral white matter diseases. This review highlights the morphology, pathogenesis, clinical and neuroimaging diagnosis of hypertensive SDIs, and their differential diagnosis with atherosclerotic SDIs in the historical aspect. It is emphasized that the lacunar state of the brain in hypertension is a predictor of massive cerebral hemorrhages. Special attention is paid to current studies of the morphology and pathogenesis of diffuse changes in white matter and to the role of blood-brain barrier impermeability in the development of progressive leukoencephalopathy.

[Lacunar stroke]. / Lakunarnyi insul't.

Lacunar stroke occupies a special place among the various subtypes of ischemic stroke, accounting for about 25% in its structure and pathogenetically most often associated with cerebral microangiopathy caused by arterial hypertension (AH) and stenotic tandem atherosclerosis (AS) of cerebral arteries. Small deep (lacunar) infarction (SDI) of the brain is its structural basis. In recent years, understanding of its heterogeneous pathogenesis, clinical and practical significance was significantly expanded in connection with the widespread introduction into practice of highly informative neuroimaging methods (first of all, the newest MRI methods), which make it possible to identify SDI of the brain at various stages of their development, including in the acute period of lacunar stroke. This review covers in the historical aspect the issues of morphology, pathogenesis, clinical and neuroimaging dynamics of hypertensive and atherosclerotic SDI, including the criteria for their differential diagnosis. Particular attention is paid to the problems of asymptomatic ('silent') SDI, which, according to recent research, along with the diffuse pathology of the cerebral white matter, make a large contribution to the development of cognitive impairment up to the development of vascular dementia, and also are predictors of severe hemorrhagic and ischemic stroke in patients with AH and AS.

[Relation between ultrasonographic and morphological characteristics of atherosclerotic plaques of carotid sinus]. / Sviaz' ul'trazvukovykh i morfologicheskikh kharakteristik ateroskleroticheskikh bliashek karotidnogo sinusa.

The authors revealed relation between the structure of an atherosclerotic plaque (ASP) and intensity of the ultrasound signal reflected form the ASP. Our prospective pilot study included a total of 90 patients (71 men and 19 women aged from 47 to 79 years, with the median age 62 years) presenting with atherosclerotic stenosis of the carotid sinus (CS) and undergoing treatment at the Research Centre of Neurology (Moscow) from April 2015 to March 2016. All patients underwent ultrasonographic examination followed by morphological study of the structure of the plaques removed during carotid endarterectomy (CEA). It was revealed that intensity of the ultrasound signal from an ASP depended on the morphological structure of the ASP components: the foci of atheromatosis were associated with an ultrasound range of 1.1-5.6 dB, those of fibrosis - with the range 23.1-30.5 dB, and those of calcinosis - with the range 42.3-44.7 dB (presented are the values from the 15th to 85th percentiles). It was determined that an increase of intensity of the ultrasound signal reflected from the foci of atheromatosis and fibrosis in the ASP was associated with the presence of small calcificates therein, and a decrease of intensity of the ultrasound signal from the portions of fibrosis in the ASP - with large accumulation of lipophages or newly formed vessels in these portions.

Neovascularization of Carotid Atherosclerotic Plaque and Quantitative Methods of Its Dynamic Assessment in Vivo.

The study demonstrates significant variety of neovascularization degree and vessel diameter in the carotid atherosclerotic plaque. It is suggested that the increase in the number of vessels with a diameter <20 µ can be indicative of increased atherosclerosis activity, while the increase in the number of vessels with a diameter ≥40 µ indicates "reparative potential" of plaques. Duplex contrast-enhanced ultrasound scanning allows characterization of the localization and number of vessels with a diameter of ≥30 µ in the plaque, while even slight elevation of plasma concentration of basic fibroblast growth factor attests, first of all, to increased content of small vessels <30 µ in the plaque. The level of fibroblast growth factor >1.5 pg/ml is a reliable marker of increased number of both small and large vessels in the plaque.

[Multifocal central nervous system lymphoma misdiagnosed as acute disseminated encephalomyelitis]. / Pervichno-mnozhestvennaia limfoma tsentral'noi nervnoi sistemy, oshibochno diagnostirovannaia kak ostryi rasseiannyi éntsefalomielit.

Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal non-Hodgkin lymphoma. Difficulties in diagnosing PCNSL are associated with the absence of pathognomonic clinical and neuroimaging findings of this disease. The article describes the clinical case of a female patient with autopsy-confirmed multifocal large-cell B-cell CNS lymphoma misdiagnosed as acute disseminated encephalomyelitis (ADEM). Clinical and neuroimaging characteristics of PCNSL and ADEM as well as the role of diagnostic methods in establishing the correct diagnosis are discussed.

[Intimal rupture of the displastic middle cerebral artery wall complicated by thrombosis and fatal ischemic stroke]. / Razryv intimy pri displazii stenki srednei mozgovoi arterii, oslozhnivshiisia trombozom i razvitiem tiazhelogo ishemicheskogo insul'ta.

The authors present a clinical-morphological observation of the 47-year old man with a severe fatal ischemic stroke due to middle cerebral artery thrombosis which developed at the site of intimal rupture. The cause of intimal rupture was the arterial wall dysplastic changes. There were no signs of atherosclerosis and hypercoagulation. As the intima rupture did not lead to blood input into arterial wall, but was accompanied by superimposed thrombosis, we suggested to denote such cases as incomplete dissection.

[Morphometric characteristics of neovascularization of carotid atherosclerotic plaques]. / Morfometricheskaia kharakteristika neovaskuliarizatsii ateroskleroticheskikh bliashek karotidnogo sinusa.

OBJECTIVE: to identify the relationship between the magnitude of neovascularization of an atherosclerotic plaque and its other processes, such as atheromatosis, macrophage responses, hemorrhages, and calcification. MATERIAL AND METHODS: 48 carotid atherosclerotic plaques all their way underwent morphopathological examination, by assessing the magnitude of neovascularization (total vessel density per plague cm2; density of vessels of different diameters; localization in section), atheromatosis (a volume fraction), foam cells (a score of 0 to 5), hemorrhages (a score of 0 to 4), and calcification (a score of 0 to 4). The Mann-Whitney U test and the Spearman correlation coefficient with p<0.05 were used in the statistical analysis. RESULTS: There was a substantial variability in vessel diameters and densities in the plaque with a drastic predominance of vessels smaller than 20 µm in diameter (69.8±14.3%). The vessels with a diameter as large as 20 µm were more frequently located in the area of accumulation of foam cells or organizing hemorrhages (p<0.03), unlike those with a diameter of more than 40 µm, which were more common in the areas of connective tissue, especially adjacent to large calcifications, and in the foci of organized hemorrhages (p<0.008). Intensified calcification was accompanied by the higher density of vessels having a diameter of more than 40 µm (p<0.038) and particularly of those with a diameter of more than 60 µm (p=0.006). The degree of hemorrhages and the number of foam cells were unrelated to the density of vessels, but these increased with their localization in the surface areas of a plaque (p=0.000342). With the increasing severity of atheromatosis, there was a decrease in the density of vessels larger than 20 µm in diameter (p=0.00042). CONCLUSION: The number, diameter, and location of vessels in the plaque serve as a dynamic reflection of its destructive and reparative processes; and a larger number of vessels having a diameter of more than 40 µm can be an indicator for the activation of reparative processes.

[Actual problems of brain pathology in cerebral microangiopathy]. / Aktual'nye problemy patologii golovnogo mozga pri tserebral'noi mikroangiopatii.

Cerebral microangiopathy (small vessels disease) is a cause of diffuse changes of brain tissue (encephalopathy) denoted in Russian literature by the term dyscirculatory encephalopathy (DE). The main cause of microangiopathy leading to encephalopathy is arterial hypertension, less frequently - cerebral amyloid angiopathy and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The diagnosis of encephalopathy in patients with microangiopathy is based on the combination of clinical manifestations (mainly, cognitive impairment of varying severity and disorders of gait) with the neuroimaging changes (white matter hyperintensity, multiple lacunar infarcts on MRI). The causes of DE hyperdiagnosis in Russia, its differential diagnosis with the consequences of recurrent strokes as well as the question of the terminology are considered. The term 'microangioencephalopathy' (instead of DE) to denote encephalopathy in patients with the cerebral small vessel disease is proposed, as more fully reflecting morphological changes of the brain.

[Cerebral infarctions in vertebrobasilar artery atherosclerosis]. / Infarkty golovnogo mozga pri ateroskleroze arterii vertebrobaziliarnoi sistemy.

AIM: to obtain more specific information on the morphology and pathogenesis of cerebral infarctions occurring in vertebrobasilar artery (VBA) atherosclerosis. MATERIAL AND METHODS: Macro- and microscopic investigations of the brain, its arterial system, and heart were conducted in 69 autopsy cases with infarctions located in the vertebrobasilar system (VBS) in atherosclerosis. RESULTS: 69 cases were found to have 206 VBA infarctions of various extent and locations. The detected infarctions were single and multiple in 27 and 42 cases, respectively. The detected infarctions included extensive (n=7), large (n=9), medium (n=63), small deep (lacunar) (n=97), and small superficial (n=30). The brain stem showed lacunar infarctions most frequently (76% of the infarctions at this site). Medium and small infarctions were identified at the same frequency in the cerebral hemispheres and cerebellum. The occurrence of 94% of the extensive and large infarctions was ascertained to be pathogenetically associated with atherothrombotic occlusion of the intracranial arteries in the VBS. 76% of the small infarctions occurred through the mechanism of cerebral vascular insufficiency in tandem atherostenosis of VBAs in conjunction with an additional decrease in cerebral blood flow under the influence of an extracerebral factor (coronary heart disease). Medium infarctions were approximately equifrequently due to the two aforementioned causes and, in some cases, to cardiogenic thromboembolism of VBAs. Infarctions were multiple in most cases; while recent large atherothrombotic infarctions were frequently concurrent with small organized infarctions resulting from tandem atherostenosis of VBAs. CONCLUSION: This investigation could establish the relationship between the site, extent, and pathogenetic factors of infarctions in the VBA bed in atherosclerosis, as well as the prognostic value of small infarctions as predictors for severe ischemic stroke.

[Internal carotid artery dissection as a cause of severe ischemic stroke with lethal outcome]. / Dissektsiya vnutrennei sonnoi arterii kak prichina tyazhelogo ishemicheskogo insul'ta s letal'nym iskhodom.

We present a medical history of a 30-year old male patient with fatal ischemic stroke, resulting from the right internal carotid artery (ICA) dissection provoked by repeated head tilts and verified by magnetic resonance imaging and pathomorphological examination. At admission, the high level of creatine phosphokinase (5284 un/ml, normal level<171) in the blood was found, the coagulation parameters were normal. Autopsy revealed intramural hematoma (IMH), which was located between the media and adventitia of the arterial wall, began at 3 cm above the common carotid artery bifurcation and extended to the base of the skull. The lumen of the ICA at the level of the IMG and intracranial parts as well as of the middle cerebral artery was occluded by the thrombus. The histological examination of the right ICA wall found splitting, thinning, fragmentation, disrupters of internal elastic membrane, severe media fibrosis, myocyte necrosis at the site of the dissection with the surrounding leukocyte infiltration, as well as lymphocytic infiltrates, clusters of eosinophils in adventitia. Similar changes, except myocyte necrosis, were also found in intact (non-dissected) brain supplying arteries. In general, they were similar to those in fibromuscular dysplasia (FMD). Histochemical and electron microscopic studies of skeletal muscles showed signs of mitochondrial cytopathy. The authors discuss the relationship between the dissection, FMD and mitochondrial pathology.

Disorders of higher mental function due to single infarctions in the thalamus and in the area of the thalamofrontal tracts.

Nine patients (five female and four male, mean age 58 years) with small infarcts in the thalamus (TH) or in the region of the thalamofrontal tracts and producing acute mental disturbances which in the acute phase of insult consisted of dementia in seven cases and mild cognitive disturbances in two cases. The complex of mental changes was similar to that seen in "frontal syndrome" and was characterized largely by lack of spontaneity, adynamia, disorientation, loss of attention and memory, slowing of all mental processes, and lack of criticality and adequacy. Accompanying focal neurological symptoms were mild in seven patients and moderate or pronounced in two. In five patients, the severity of mental disturbances decreased with time. Computer tomography demonstrated small infarcts in the anterior or medial parts of the TH in seven patients and in the posteromedial parts of the anterior limb of the internal capsule, i.e., the thalamofrontal tracts, in two cases. In five cases, infarcts were located in the dominant hemisphere, with lesions in the non-dominant hemisphere in three and in both hemispheres in one. The positions of all foci corresponded to structures traversed by pathways connecting the TH and the lower part of the reticular formation to the frontal lobes. It is suggested that disconnection of these pathways leads to cognitive lesions or dementia because of functional inactivation of the frontal cortex.