[Pseudotumorous form of primary central nervous system vasculitis]. / Psevdotumoroznaya forma pervichnogo vaskulita tsentral'noi nervnoi sistemy.

A 23-year-old female patient with primary vasculitis of the central nervous system simulating a brain tumor is described. The clinical picture was represented by migraine-like headaches, ataxia, transient numbness of the right leg, the lips, double vision, a slight decrease of cognitive functions. MRI of the brain revealed a tumor-like focus in the cerebellum, intensively accumulating contrast, containing micro-hemorrhages (SWI mode). Small single ischemic foci in the brain hemispheres and brain stem were also found. MR angiography (3T) did not found any pathology. Examination of the cerebrospinal fluid revealed a small cytosis (mainly T-lymphocytes) and a slight increase in protein. The results of the analysis of cerebrospinal fluid for syphilis, tuberculosis and the herpetic group of viruses were negative, type 1 oligoclonal synthesis was found. Blood tests for toxoplasmosis, antibodies to aquaporin, anti-neutrophil antibodies, markers of systemic inflammation were within normal limits. Different diagnoses were assumed: demyelinating disease, encephalitis, multiple encephalomyelitis, lymphoma. The diagnosis was established only by a brain biopsy - lymphocytic vasculitis was revealed. According to the immunohistochemical study, T-helpers predominated in the infiltrates. After pulse therapy with Metylprednisolon (1000 mg intravenously drip №. 5), the patient's condition almost returned to normal. It was recommended to take prednisolone per os (starting dose 60 mg) for 7 months.

[Reversible cerebral vasoconstriction syndrome and ischemic stroke]. / Sindrom obratimogo tserebral'nogo vazospazma i ishemicheskii insul't.

The article describes a 45-year-old female patient with recurrent transient ischemic attacks and ischemic stroke due to spontaneous spasm of the middle cerebral artery, the anterior cerebral artery and distal part of the internal cerebral artery on the left, verified by MR angiography and CT angiography. It is assumed that the spasm caused damage to the vascular wall, an increase in its permeability, the development of edema, inflammation and subsequent fibrosis, therefore a complete restoration of the arterial lumen did not occur.

[Moyamoya disease and syndrome]. / Bolezn' i sindrom moyamoya.

Moyamoya disease (MMD) is a rare disease characterized by progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the proximal part of their branches, which is accompanied by the formation of collateral network that look like smoke clouds on angiography (Japanese terminology - moyamoya). If the disease is comorbid to other diseases, usually associated with acute or chronic inflammation, including autoimmune processes, it is designated as moyamoy syndrome (MMS). MMD and MMS are one of the causes of ischemic stroke and chronic cerebrovascular insufficiency in young and middle age, less often they lead to hemorrhages. The review presents data on epidemiology, morphology, pathogenesis (the role of genetic predisposition, inflammation, proangiogenic factors and immune disorders), clinical manifestations, instrumental diagnostics and treatment.

[Transforming growth factor beta in patients with cervical artery dissection]. / Transformiruyushchii faktor rosta beta u bol'nykh s dissektsiei vnutrennikh sonnykh i pozvonochnykh arterii.

OBJECTIVE: To evaluate transforming growth factor beta (TGF-ß) in patients with cervical artery dissection (CeAD). MATERIAL AND METHODS: TGF-ß was studied by enzyme immunoassay in 74 of 336 patients with CeAD observed at the Research Center of Neurology (Moscow) from 2000 to 2021. The average patient's age at the time of TGF-ß study was 41.6±9.8 years; the proportion of women was 51%. TGF-ß was studied in the first month of the disease (n=9), for 2-3 months (n=12) and at a later period (mean - 4.3±5.03 years) (n=53). The control group consisted of 20 healthy volunteers, matched for age and sex. Dissection occurred in internal carotid artery (ICA) (n=42), vertebral artery (VA) (n=29), ICA+VA (n=3) and involved 1 artery (n=58) or 2-3 arteries (n=16). Clinical manifestations included ischemic stroke (IS) (n=49), isolated cervical-cephalic headache (n=23), lower cranial nerve palsy (n=2). Pathological CeAD tortuosity was detected by angiography in 13 patients, and a dissecting aneurysm in 15 patients. RESULTS: TGF-ß1 and TGF-ß2 were elevated in patients with CeAD patients compared with the control: TGF-ß1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p=0.001; TGF-ß2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p=0.001. The highest TGF-ß1 and TGF-ß2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-ß level and various clinical and angiographic parameters. CONCLUSION: Increased TGF-ß level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-ß level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-ß can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

[Cervical artery dissection in women: relationships with pregnancy and postpartum period]. / Dissektsiya vnutrennei sonnoi i pozvonochnoi arterii u zhenshchin: vzaimootnoshenie s beremennost'yu i poslerodovym periodom.

OBJECTIVE: To study the frequency of CeAD that developed during pregnancy or in post partum period among all CeADs in women; to study the course of pregnancy in women with prior CeAD. MATERIAL AND METHODS: 162 women (mean age 37.1±4.1 years) with CeAD we examined at the Research Center of Neurology (Moscow), 98% women were studied during last 15 years. 140 women were of childbearing age (≤45 years, mean age - 35±2.8 years). All patients were interviewed whether or not CeAD occurred during pregnancy or in post partum period (CeADPPP). Obstetric history before and after CeAD was studied in 57 women of childbearing age (average age - 35.9±7.3 years at CeAD development). RESULTS: CeADPPP developed in 6 out of 162 all female patients (3.7%) or of 140 childbearing age patients (4.3%). It occurred 2-6 months (4 patients) and 10 days after delivery (1 patient), or on the 25th week of pregnancy (1 patient). CeADPPP patients were younger than patients with CeAD out of pregnancy or postpartum period (29.8±8 years vs 35.1±6.7 years, p>0.05). CeADPPP in comparison with CeAD outside these periods more often involved internal carotid artery (ICA) (50% vs 35%, p=0.666), more often occurred in 2-3 arteries (50% vs 31%, p=0.386) and more often was accompanied by dissecting aneurysm development (50% vs 8%, p=0.013). After CeAD, 18 out of 57 patients in whom obstetric history was studied, including 3 patients with postpartum dissection had 29 pregnancies. The pregnancy outcomes were as follows: childbirth (17 pregnancies, 59%), fetal loss (8 pregnancies, 27%) and medical abortion (4 pregnancies, 14%). Delivery occurred on average 4.5±2.061 years after CeAD in women aged 33.0±4.25 years (cesarean section - 15 patients). Fetal loss occurred at 7.4±3.5 weeks of pregnancy in women aged 37.6±3.13 years on average 2.7±1.4 years after CeAD. Fetal loss frequency after CeAD was higher than before it (27% vs 7%, p=0.016). There were no CeAD recurrences during pregnancy and postpartum period in women who had previously undergone CeAD. CONCLUSION: CeADPPP frequency among all dissections in women is 3.7-4.3%. The risk of CeAD recurrence during pregnancy or the postpartum period after prior CeAD is very low. The risk of fetal loss during 2.7±1.4 years after CeAD is higher than before it (27% vs 7%). Hormonal and growth factors associated with pregnancy and the postpartum period is suggested to contribute to cervical artery wall damage. It is possible that the prolonged action of some of these factors may disrupt the placental vessels formation, predisposing to miscarriage.

[Internal carotid artery dissection in patients with Turner's syndrome]. / Dissektsiya vnutrennei sonnoi arterii u bol'nykh s sindromom Shereshevskogo­Ternera.

Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.

[Primary vasculitis of internal carotid and vertebral arteries: a role of cytokines, transforming growth factor beta 1 and basic fibroblast growth factor]. / Pervichnyi vaskulit vnutrennei sonnoi i pozvonochnoi arterii: rol' tsitokinov, transformiruyushchego faktora rosta ß1 i osnovnogo faktora rosta fibroblastov.

OBJECTIVE: To study clinical/laboratory signs of primary vasculitis (PV) of the internal carotid artery (ICA) and vertebral artery (VA). MATERIAL AND METHODS: We examined 31 patients (23 men, 74%, mean age - 36.2±5.7 years) with ICA/VA PV verified by vessel wall contrast enhancement on black blood MRI (T1-weighted fat and blood suppressed sequences with- and without contrast injection) at the Research Center of Neurology (Moscow) from January 2012 to September 2019. Systemic vasculitis was excluded in all cases. Interleukins (IL-1ß, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-ß1) and basic fibroblast growth factor (bFGF) were analyzed by ELISA in 25 patients. Control group consisted of 21 healthy volunteers (12 men, 57%; mean age - 35.3±10.2 years). RESULTS: Clinical manifestations of ICA/VA PV included: ischemic stroke (IS) (94%), which combined with transient ischemic attacks (TIA) in 35%; isolated TIA (3%); Tolosa-Hunt syndrome (3%). Recurrent strokes were observed in 41% of patients on average in 5.3±2.1 months. Carotid artery was involved in 77%, VA - in 16%, both arteries - in 7%. Concomitant involvement of ICA/VA branches was in 19% patients. The level of arterial damage was follows: Intracranial part of arteries involved in 55%, intra-extracranial - in 35%, extracranial - in 10%. Bilateral involvement was found in 26%. Headache/neck pain in the acute IS period was observed in 21%. IS severity (NIHSS) was as follows: moderate (59%), mild (34%), moderately severe (7%). Disability after 3 months according to mRankin scale was as follows: mild (72%) moderate (21%), none (7%). The laboratory study revealed an increased levels of IL-6 (8.19±3.89 pg/ml vs 4.7±1.48 in control, p=0.000), IL-2 (5.64±1.82 pg/ml vs 4.30±1.65, p=0.013), TNF-a (36.9±33.66 pg/ml vs 12.68±5.93, p=0.000), TGF ß1 (2.77±1.60 pg/ml vs 1.63±0.64, p=0.006) and bFGF (417.67±132.68 pg/ml vs 335.71±105.08, p=0.018). The levels of IL-1ß and IL-17 did not differ significantly from the control. CONCLUSION: ICA/VA PV has a number of clinical peculiarities. Proinflammatory cytokines produced by Th17 and Th1 CD4+ lymphocytes as well as bFGF and TGR-ß1 play a role in its pathogenesis. Normal levels of IL-1ß and IL-17 suggest that they are not significant in the development of isolated inflammation in ICA/PA, in contrast to systemic inflammation in giant cell arteritis, in which, according to literature data, their level increases. Isolated ICA/PA inflammation seems to be caused by transaxonal (trigeminal nerve, upper-cervical roots, autonomic nerves) spread of pathogens that initiate immune inflammation in the ICA/PA wall.

[Salt sensitivity and osmotic fragility are newly specified risk factors for age-related cerebral microangiopathy]. / Sol'-chuvstvitel'nost' i osmorezistentnost' ­ faktory riska vozrast-zavisimoi tserebral'noi mikroangiopatii.

AIM/: To assess individual values of salt sensitivity and osmotic fragility on the patient's erythrocytes and evaluate predictive ability of these parameters in the development of cerebral small vessel disease (CSVD). MATERIAL AND METHODS: The study included 73 patients with CSVD (48 women, mean age 60.1±6.5 years) and 19 volunteers (14 women, mean age 56.9±5.4 years). Their erythrocytes were used for the measurement of salt-sensitivity by a modified salt blood test and of osmotic fragility by the classical osmotic fragility test. Binary logistic regression was used to assess the ability of salt-sensitivity and osmotic fragility to predict CSVD development. ROC analysis was used to find out the optimal threshold values of these predictors, their sensitivity and specificity. RESULTS: An increase in salt sensitivity (cut-off: 8.5 mm/h; sensitivity 64%, specificity 74%) and osmotic fragility (cut-off: 0.62 u.a.; sensitivity 52%, specificity 90%) or their simultaneous use (p of the model <0.000001, cut-off 0.62; sensitivity 88%, specificity 68%) are the independent predictors of CSVD. An increase in salt sensitivity and osmotic fragility is also independently associated with the acceleration of severity of white matter hyperintensities according to Fazekas stages (p=0.019 and 0.004, respectively). CONCLUSION: The possibility of prediction of CSVD according to an increase in salt sensitivity and osmotic fragility allows us to consider them as the risk factors of CSVD. The standardization of these tests for use in clinical practice is necessary to identify the risk group for CSVD and its individual prevention.

[Aneurysms and pathological tortuosity of the internal carotid and vertebral arteries in patients with dissection of these vessels: a results of long-term study]. / Anevrizmy i patologicheskaya izvitost' vnutrennikh sonnykh i pozvonochnykh arterii u bol'nykh s dissektsiei etikh sosudov: rezul'taty dolgosrochnogo issledovaniya.

OBJECTIVE: To study the frequency, angiographic and clinical features of aneurysms and tortuosity (T) in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection. MATERIAL AND METHODS: Three hundred and twenty-seven patients (average age - 37.8±9.1 years, women - 57%) with ICA/VA dissection verified by neuroimaging were studied. Repeated neuroimaging in 2.4±3.3 years was performed in 254 patients. In one case, tortuous ICA fragment resected at the surgery complicated by dissection was histologically studied. RESULTS: ICA/VA aneurysms were found in 46 (14%) patients. At repeated neuroimaging aneurysms did not change (38%), increased (11%) or decreased in size (8%), were not detected (38%) or were detected for the first time (5%). Patients with aneurysms compared with those without aneurysms more often had multiple dissections (44% vs. 20%, p=0.001) and T (35% vs. 13%, p=0.001), but less frequently the artery lumen occlusion in the acute period (15% vs. 40%, p=0.001). T was found in 53 (16%) patients. Patients with T compared with patients without T were older (40.6±8.1 vs. 37.3±9.3 years, p=0.039), more often had aneurysms (30% vs. 11%, p=0.001) and recanalization of occlusion observed in the acute period (89% vs. 54%, p=0.006). Dissection more often occurred in tortuous than in non-tortuous artery (79% vs 21%, p=0.001). During 4.8±3.6 years of follow-up, TIA developed inone patient (2%) with an aneurysm. Histological examination of tortuous ICA fragment, which also contained a small aneurysm, revealed dysplastic changes. CONCLUSION: The association between aneurism and T in patients with ICA/VA dissection suggests their common basis - the arterial wall weakness due to dysplasia. Age-related changes are also important for T development. T is a risk factor for ICA/VA dissection. Aneurysms formed after ICA/VA dissection have a benign course.

[Fibromuscular dysplasia and its neurological manifestations]. / Fibromyshechnaya displaziya i ee nevrologicheskie proyavleniya.

The authors present the current data on the classification, epidemiology, etiology, neurological manifestations, prognosis, diagnosis, and treatment of patients with fibromuscular dysplasia (FMD). The review is based on the selection of publications by searching PubMed for keywords from the first sources until March 2019. FMD is a segmental non-atherosclerotic and non-inflammatory disease of large- and medium-caliber arteries leading to their stenosis. The disease occurs mostly in women (90%), and manifests itself in the 5th decade of life. In the cerebrovascular form of FMD, the extracranial internal carotid artery and the vertebral artery are usually affected. Diagnosis is based on the identification of alternation of narrowing and dilation of arteries using angiography (the string of beads sign (multifocal form)). Neurological manifestations include headache, tinnitus, and ischemic stroke, usually due to the dissection or stenosis, rarely, intracerebral or subarachnoid hemorrhages. The prognosis in most cases is favorable, relapses of strokes are rare. Treatment includes antiplatelet agents, if they are ineffective to prevent recurrence of ischemic stroke, endovascular treatment is carried out. Approaches to the treatment of intracranial aneurysms do not differ from those in patients without FMD.

[Pulmonary arteriovenous shunt - a rare cause of recurrent stroke due to paradoxical embolism]. / Legochnyi arteriovenoznyi shunt ­ redkaya prichina retsidiviruyushchikh narushenii mozgovogo krovoobrashcheniya po mekhanizmu paradoksal'noi embolii.

Paradoxical embolism is one of the mechanisms of ischemic stroke in patients younger than 45 years of age, due to opening between the right and left chambers of the heart through a patent foramen ovale, an atrial or ventricular septal defect, pulmonary arteriovenous malformations (PAVMs), etc. The PAVMs are structurally abnormal vessels that provide direct capillary-free communication between the pulmonary and systemic circulations, and hence an anatomic "right-to-left" shunt. Most pulmonary malformations are congenital and associated with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease). This publication highlights the issues of pathogenesis, clinical presentation, diagnosis and treatment of this pathology, and also describes a clinical case in which multiple PAVMs caused repeated ischemic strokes.

[Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids]. / Khronicheskoe limfotsitarnoe vospalenie s perivaskulyarnym nakopleniem kontrastnogo veshchestva v mostu golovnogo mozga, otvechayushchee na lechenie steroidami.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system, mainly affecting the brain stem, cerebellum and spinal cord. The clinical picture includes gradually developing ataxia, double vision, dysarthria, pyramidal and cognitive impairment. Morphological examination reveals T-cell perivascular lymphocytic infiltration with CD4 lymphocytes predominance over CD8 lymphocytes. The cause of the disease is unknown. The article describes two patients (a 18-year-old woman and a 40-year-old man) with typical clinical and MRI manifestations of CLIPPERS, which was confirmed by brain biopsy in the female patient. The duration of follow-up was 3 and 7 years, respectively. Both patients survived an infection 2-3 weeks before the onset of disease that allows one to discuss its role in CLIPPERS pathogenesis. Both patients had a clear clinical and MRI responsiveness to steroids. In the female patient, steroids were replaced by intramuscular administration of the TNF-α blocker adalimumab. During 1,5 years of its use, there were no clinical relapses and pathological brain changes on MRI.

[Clustering of diagnostic MRI signs of cerebral microangiopathy and its relationship with markers of inflammation and angiogenesis]. / Klasterizatsiya diagnosticheskikh MRT-priznakov tserebral'noi mikroangiopatii i ee svyaz' s markerami vospaleniya i angiogeneza.

OBJECTIVE: To perform cluster analysis of MRI signs of cerebral microangiopathy (small vessel disease, SVD) and to clarify the relationship between the isolated groups and circulating markers of inflammation and angiogenesis. MATERIAL AND METHODS: The identification of groups of MRI signs (MRI types) using cluster hierarchical agglomerative analysis and iterative algorithm of k-means and assessment of their relationship with serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1-α (HIF1-α) determined by ELISA were performed in 96 patients with SVD (STRIVE, 2013) (65 women, average age 60.91±6.57 years). RESULTS: Cluster analysis of MRI signs identified two MRI types of SVD with Fazekas grade 3 of white matter hyperintensity (WMH). MRI type 1 (n=18; 6 women, mean age 59.1±6.8 years) and MRI type 2 (n=22, 15 f., mean age 63.5±6.2 years) did not differ by age, sex, severity of hypertension, presence of other risk factors. MRI type 1 had a statistically significantly more pronounced WMH in the periventricular regions, multiple lacunes and microbleeds, atrophy, severe cognitive impairment and gait disorders compared with MRI type 2. Its formation was associated with a decrease in VEGF-A level. MRI type 2 had the significantly more pronounced juxtacortical WMH, white matter lacunes, in the absence of microbleeds and atrophy, and less severe clinical manifestations compared with MRI type 1. Its formation was associated with an increase in TNF-α level. CONCLUSION: Clustering of diagnostic MRI signs into MRI types of SVD with significant differences in the severity of clinical manifestations suggests the pathogenetic heterogeneity of age-related SVD. The relationship of MRI types with circulating markers of different mechanisms of vascular wall and brain damage indicates the dominant role of depletion of angiogenesis in the formation of MRI type 1 and increased inflammation in the formation of MRI type 2. Further studies are needed to clarify the criteria and diagnostic value of differentiation of MRI types of SVD, and also their mechanisms with the definition of pathogenetically justified prevention and treatment of various forms of SVD.

[Intracerebral hemorrhage in the late period of internal carotid artery dissection]. / Vnutrimozgovye krovoizliianiia v pozdnem periode dissektsii vnutrennei sonnoi arterii.

Cervical artery dissection is the common cause of ischemic stroke in young and middle-age patients. According to our previous studies, dissection is related to arterial wall dysplastic changes, which in their turn are due to mitochondrial cytopathy. The authors describe three male patients who at the age of 53, 25 and 35 years underwent internal artery (ICA) dissection with occlusion of its lumen and subsequent recanalization in one of them. In 3.5 months, 13.5 years and 3 years respectively, patients developed intracerebral hemorrhage (IСH), which was not related to arterial hypertension, cerebral arterial aneurysms and anticoagulants. IСH were located on the side of ICA occluded after dissection (2 patients) or bilaterally in the territory of patent ICA (1 patient). Multivoxel 1H-MR spectroscopy performed in one patient on 40 and 48 days after ICH revealed a high lactate peak in the externally unchanged hemispheric white matter. It is assumed that mitochondrial cytopathy in patients with dissection may involve large as well as small intracerebral arteries (mitochondrial microangiopathy), which could be the cause of ICH.

[Primary central nervous system vasculitis]. / Pervichnyi vaskulit tsentral'noi nervnoi sistemy.

Primary vasculitis (angiitis) of the central nervous system (PACNS) is a rare disease targeting the vessels of the brain, spinal cord and leptomeninges without systemic involvement. The etiology is not clear enough. The authors review clinical, laboratory and radiological features of PACNS. Clinical manifestations are variable and depend on the caliber of affected vessels. The main clinical manifestations of small sized vessel vasculitis include encephalopathy (cognitive disorders, epileptic seizures), headache and transient cerebral ischemia. The main clinical presentation of vasculitis of medium/large cerebral arteries is ischemic strokes, which usually develop in different vascular territories. CSF findings in the majority of patients show modest lymphocytic pleocytosis, elevated protein level and occasionally the presence of oligoclonal bands. MRI data are not specific and include infarcts, hyperintensity (FLAIR) and sometimes tumor-like lesions. The gold standard for the verification of PACNS affected small-sized arteries is brain and leptomeningeal biopsy. Cerebral angiography allows the verification of vasculitis of medium and large cerebral arteries revealing segmental narrowings (beading). High resolution black blood MRI before and after contrast injection may visualize intracranial vessel wall contrast enhancement - the sign of inflammation in intracranial arteries. Treatment of PACNS includes corticosteroids and cyclophosphamide. In the case of patient intolerance, rituximab and blockers of tumor necrosis factor may be used.

[The role of arterial, venous blood and cerebrospinal fluid flow disturbances in forming cognitive impairment types in age-related cerebral microangiophathy]. / Rol' narushenii arterial'nogo, venoznogo krovotoka i likvorotoka v formirovanii kognitivnykh rasstroistv pri vozrastzavisimoi tserebral'noi mikroangiopatii.

BACKGROUND: Age-related cerebral microangiopathy (small vessel disease, SVD) is the main cause of vascular and mixed cognitive impairment (CI) with a complex neuropsychological profile. AIM: To investigate the role of arterial and venous blood flow and cerebrospinal fluid (CSF) flow, as well as their interrelation, in the forming of CI types in patients with SVD. MATERIAL AND METHODS: Fifty patients (31 f., mean age 61.2±6,2) with SVD (STRIVE, 2013), including 37 with mild CI and 13 with dementia, were examined. A type of CI was determined based on combination of standard deviations from normal results on memory and executive function tests: isolated dysexecutive (13) and predominantly dysexecutive (6), predominantly amnestic (12), mixed, equal impairment of EF and memory, (19). In the statistical analysis, groups of the isolated and predominantly dysexecutive types were merged according to the dominance of deviations in the EF into the dysexecutive type of CI (19). Phase contrast MRI (PhC-MRI) was used to assess characteristics of arterial and venous blood flow and CSF flow on different levels. Indexes of pulse and intracranial compliance and surface of the cerebral aqueduct were calculated. RESULTS: Patients with all CI types had a CSF flow systolic peak delay at the cervical level. Mixed and dysexecutive CI types as compared with predominantly amnestic type and control were defined by blood flow reduction in the sinus rectus, and mixed type by the additional decrease in its pulse wave width, blood flow reduction in an internal jugular artery and maximal blood flow velocity in the inner carotid artery, the increase in the intracranial compliance index and surface of the cerebral aqueduct. CONCLUSION: The neuropsychological CI type in SVD is defined by features of pathophysiological mechanisms conditioned on differences in blood flow and CSF flow impairment severity and formed hydrodynamic interaction between them. Differential features of CI types in SVD defined by PhC-MRI might become important predictive indicators of potential interaction between SVD and degeneration, improve understanding of risk factors, pathogenesis, prevention and treatment of age-related brain damage.

Hypertension and Cerebral Microangiopathy (Cerebral Small Vessel Disease): Genetic and Epigenetic Aspects of Their Relationship.

Hypertension (HT) and its cerebral complications are extremely vexing medical and social problems. Despite the obvious association between hypertension and the clinical and neuroimaging features of cerebral microangiopathy (CMA) (also known as cerebral small vessel disease), the causal links between them remain ambiguous. Besides, antihypertensive therapy as the only way to manage these patients does not always prevent brain damage. Knowledge about the key factors and mechanisms involved in HT and CMA development is important for predicting the risk of cerebral complications and developing new approaches to their prevention and treatment. At present, genome-wide association studies and other approaches are used to investigate the common hereditary mechanisms of HT and CMA development, which will explain a large number of CMA cases not associated with hypertension, lack of a correlation between HT severity and the degree of cerebral injury, and failure of antihypertensive therapy to prevent CMA progression. Epigenetic markers likely play a modulating role in the development of these diseases.

[Anamnestic headache in patients with cervical artery dissection: clinical characteristics and pathogenetic mechanisms]. / Anamnesticheskaia golovnaia bol' u bol'nykh s dissektsiei magistral'nykh arterii golovy: klinicheskie osobennosti i mekhanizmy razvitiia.

AIM: To study the frequency and characteristics of headache which is in the past history (HPH) of patients with cervical artery dissection (CeAD) and evaluate with the help of EEG and visual evoked potentials (VEP) the role of central mechanisms in its development. MATERIAL AND METHODS: Two hundred and twenty-seven patients with CeAD verified by neuroimaging were studied. All patients were interviewed about the presence of a headache in the past history and its features. The comparison group comprised 35 patients (mean age - 32,3±8,9 years, 77% female) with migraine. Thirty-five patients with HPH and 35 patients of the comparison group underwent EEG and VEP. RESULTS: HPH was found in 101 patients (average age of 38.5±8.5 years, 70% female) (44.5%) out of 227 patients. In 35 patients (15.4%), HPH met the International Criteria for migraine (with aura - 3.1%, without aura - 12.3%) and in 66 patients (29.1%) did not (non-migraine headache). The latter started at the age of 24.5±10.2 years, had mild/ moderate intensity (95%), diffuse localization (68%), dull/pressing/squeezing character (53%), never accompanied by vomiting and rarely by nausea (8%), photo- phonophobia (11%). HPH, which met the migraine criteria unlike migraine in the comparison group began at a later age (19.9±9.6 vs 16.2±4.4 years, p<0.03), more frequently did not have aura (80% vs 48%, p<0.003), less often was unilateral (31% vs 71%, p<0,004) and had less intensity. The visual EEG analysis less often found rhythmic disorganization in CeAD patients with HPH than in comparison group with migraine. The hyperventilation caused a slight increase in the spectral power of Teta, Delta waves in HPH patients and significant enhancement in comparison group with migraine (p<0.05). Pattern reversal VEP in patients with HPH had a greater latency and smaller amplitude of cortical responses than in comparison group with migraine (p=0.028 and =0.037, respectively). The flash VEP amplitude was lower in HPH patients than in migraine (p=0.01). CONCLUSION: HPH in patients with CeAD meets criteria of migraine in 15.4% (with aura - 3.1%, without aura - 12.3%), 29.1% patients have nonmigraine HPH. Central mechanisms, namely, the hypersensitivity of the cerebral cortex playing the main role in migraine pathogenesis, are not significant in HPH genesis. The main role appears to have peripheral mechanisms - dysplastic changes in the wall of extra- and intracranial arteries that predispose both to headache and dissection.

[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.

[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.