[Arterial hypertension and cerebrovascular pathology. Current status of the problem]. / Arterial'naia gipertoniia i tserebrovaskuliarnaia patologiia: sovremennyi vzgliad na problemu.

In the process of development and progression of arterial hypertension hypertensive cerebral angiopathy is formed - that is a complex of intricate primarily destructive (acute and recurring) and secondary reparative changes and adaptive processes occurring on all structural and functional levels of cerebral vascular system. Arterial hypertension in patients with cerebrovascular diseases should be treated. Because of heterogeneity of etiology and pathogenetic mechanisms of stroke detailed assessment of the state of cerebral vessels, blood flow, circulatory and metabolic cerebral reserve is a prerequisite of effective and safe antihypertensive therapy, prevention of stroke and other complications. This excludes generalized (leveling-off) approach to treatment and prevention of various types and subtypes of stroke. A notion that hypertension is a most important, independent controllable risk factor of cerebrovascular diseases remains definitely valid. However it is far from being a single cause of stroke.

[Hypertension--main risk factor of stroke. Results of a three years register in Krasnodar]. / Arterial'naia gipertoniia--osnovnoi faktor riska insul'ta (itogi 3 let provedeniia registra v Krasnodare).

Incidence of first stroke and stroke mortality in Krasnodar in 1997-2000 were higher compared with data of similar registers in Moskva and Novosibirsk. Hospitalization rate of patients with stroke especially of those with severe stroke was low with high 28 days and 1 year mortality. Main risk factor of stroke was hypertension which in about 2 thirds of patients was classified as mild. Half of the patients with hypertension had history of hypertensive crises. Despite high level of awareness about presence of hypertension only every tenth patient received regular antihypertensive therapy which however in most cases was ineffective. One half of the patients received no antihypertensive treatment at all. Even after stroke most of the patients did not take antihypertensive drugs and antiaggregants. Results of the register show that there exists a great deal of resource for implementation of standard measures aimed at primary and secondary stroke prevention and lowering of mortality of patients with stroke.

[Progress in neurosciences: initiatives within the framework of the program "Brain Decade (1990-2000)"]. / Progress neironauk: initsiativy v ramkakh programmy "Desiatiletie mozga (1990-2000 gg.)".

The paper describes basic scientific and practical results obtained in the past decade at the Research Institute of Neurology, Russian Academy of Medical Sciences, in the following areas: cerebrovascular diseases, degenerative and demyelinating diseases of the nervous system. Particular attention is paid to the development of national criteria for brain death, a concept of structural and functional levels of the vascular system, that of brain pathology in atherosclerosis and essential hypertension, rapid methods for evaluating neuronal apoptosis, a new method for diagnosing prionic diseases caused by a classical viruses, and a new method for histochemical diagnosis of the degree of reparative peripheral nerve processes in polyneuropathies and to the discovery of two new hereditary nervous system diseases, to direct DNA diagnosis of torsion dystonia, Wilson-Konovalov disease, Friedreich's disease, to the setting up of a national representative family register and DNA data bank for monogenous hereditary diseases, to the development of indications for craniocerebral bypass of cerebral vessels in multiple occlusions of great cerebral arteries and indications for programmable plasmapheresis in a number of autoimmune diseases of the nervous system, to the development of rehabilitative programmes for stabilogram biocontrol, markers of an active embologenous atherosclerotic plaque in the arteries supplying blood to the brain, etc.

[Treatment and prevention of cognitive dysfunction in patients with arterial hypertension and atherosclerosis: results of a randomized double-blind placebo-controlled trial of cerebrolysin]. / Lechenie i preduprezhdenie rasstroistv poznavatel'noi funktsii u bol'nykh arterial'noi gipertoniei i aterosklerozom: rezul'taty randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniia tserebrolizina.

AIM: To assess therapeutic and prophylactic effect of large-dose cerebrolysin (15 ml/day for 28 days) in hypertensive and atherosclerotic patients with cognitive disorders. MATERIAL AND METHODS: Cerebrolysin was given annually (15 ml/day for 28 days) for 2 years to 42 patients in a randomized double-blind placebo-controlled study. The effect was stated by clinical status, neuropsychological and neurophysiological data. RESULTS: In mild disturbances of cognitive functions in patients with arterial hypertension and atherosclerosis courses of cerebrolysin with one-year interval produce stable improvement of subjective status, productivity of memory, attention and thinking which persist for at least a year after the course. The clinical data agree with positive trend in neurophysiological parameters of cognitive component of the response of evoked potentials P-300. CONCLUSION: A course of 28-day annual treatment with cerebrolysin (15 ml/day) of patients with mild defects of cognitive functions stabilizes the process, leads to regression of cognitive disorders predicting vascular dementia.

[Thalamic hypertensive hemorrhage]. / Talamicheskie gipertenzivnye krovoizliianiia.

We performed statistic analysis of the results of both conservative and surgical (by means of laying on the external ventricle drain--EVD) treatment of 23 patients with thalamic (medial) hypertensive hemorrhage (THH) admitted to the hospital in the first two days of the stroke's beginning. We also investigated clinical tomographic factors which had influence either on the choice of the treatment or on the prognosis of the disease. The frequency of the lethal cases in EVD-group (6 observations) was about twice lower than in analogous group of patients treated conservatively (17 cases). In conservative treatment prognostically unfavourable factors in acute period of the stroke were the following: the awakening level lower than 10 points according to Glasgow Scale, development of acute obstructive hydrocephalus, dislocation of brain stem, break of blood into cerebral ventricles (of II-IV degree), the volume of hemorrhage more than 10 ml for thalamic and thalamo-capsular location and more than 5 ml for thalamo-mesencephalic location. Monitoring of intracranial pressure in patients with THH which had factors mentioned above revealed the development of steadfast intracranial hypertension by days 5-7 maximally. The laying on EVD was indicated in patients with unfavourable signs of THH by means of ventricle drainage. The controlled decrease of intracranial pressure increased the level of awakening, meanwhile it decreased the degree of hydrochephalus and dislocation of brain stem.

[Drug methods of preventing stroke in cardiovascular diseases (a lecture)]. / Medikamentoznye metody profilaktiki insul'ta pri serdechno-sosudistykh zabolevaniiakh (lektsiia).

Basing on the results of numerous investigations it is possible to single out 4 main directions in prevention of acute failure of cerebral circulation (AFCC) in cardiovascular diseases: stroke prevention in hypertensive subjects, prevention of cardioembolic stroke in patients with cardiac arrhythmia, prevention of recurrent AFCC episodes in patients with transitory ischemic attacks and minor stroke, prevention of the stroke by inhibition of progression of carotid atherosclerosis. The best population effect in stroke prevention belongs to active detection and adequate treatment of AH because AH is involved in development of the majority of the mechanisms underlying both hemorrhagic and ischemic stroke.

[A treatment procedure for nontraumatic cerebellar hemorrhages]. / Taktika lecheniia netravmaticheskikh mozzhechkovykh krovoizliianii.

The results of surgical treatment of 12 patients with non-traumatic intracerebellar hemorrhages are analyzed in this paper. The following parameters were assessed: clinical signs and symptoms, the level of consciousness, location and size of the lesion, the brain stem deformation, the rupture of hematoma into the adjacent ventricle, and hydrocephalus. In all patients with fulminant course as well as in the majority of patients with acute or subacute course when the brain stem compression progresses and seems to be unresponsive to medical treatment, surgery is strongly indicated. Among the surgical procedures, placement of the external ventricular drainage and extensive midline suboccipital craniectomy are curative. These procedures proved to be effective in reducing the brain stem compression. Patients with chronic intracerebral hematomas are followed conservatively.

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy.

We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene.

Spinocerebellar ataxia type 1 in Russia.

Spinocerebellar ataxia type 1 (SCA1) is one form of autosomal dominant cerebellar ataxia (ADCA) caused by trinucleotide (CAG) repeat expansion within a mutant gene. We investigated 25 patients from 15 Russian ADCA families for SCA1 mutation and found an expanded CAG repeat in 5 families. Mutant chromosomes contained 41-51 CAG repeats (mean 46.1, SD 3.1), and normal chromosomes displayed 21-27 repeat units (mean 24.7, SD 1.3). Progressive cerebellar ataxia in our series of SCA1 patients was very commonly associated with dysarthria (in all cases) and pyramidal signs (in 10 of 11 cases). In three patients from one family we found optic atrophy, which has never been described before in genetically proven cases of SCA1. We observed no specific clinical features distinguishing SCA1 from non-SCA1 patients. In contrast to the high frequency of SCA1 in our series, we found no patients with Machado-Joseph disease, another form of ADCA caused by expanded CAG repeat.

[Molecular genetic analysis--a new stage in the study of hereditary diseases of the central nervous system]. / Molekuliarno-geneticheskii analiz--novyi étap v izuchenii nasledstvennykh zabolevanii tsentral'noi nervnoi sistemy.

Molecular genetics is currently the most powerful tool for studying hereditary diseases of the central nervous system: Huntington's disease, dopa-nonresponsive dystonia, Friedreich's disease, etc. The review presents the most important results obtained in this field by the Department of Neurogenetics, Institute of Neurology, in collaboration with several Russian and foreign research institutes. The authors were the first to perform a molecular analysis of mutations and haplotypes in Huntington's disease, dopa-nonresponsive dystonia, Wilson's disease and studied the frequencies of various mutations and main genotype-phenotype correlations in the Russian population. The first direct diagnosis of Huntington's disease in Russia, as well as indirect diagnosis of Friedreich's disease, dopa-nonresponsive dystonia and Wilson's disease have been made. The authors began to investigate trinucleotide repeat expansion in dominant spinocerebellar ataxias and related disorders. The Department of Neurogenetics collected a valuable bank of DNA samples, which is sufficient to perform linkage analysis in essential tremor, novel forms of congenital cerebellar atrophy and progressive muscular atrophy.

[Clinical angioneurology on the border of the centuries]. / Klinicheskaia angionevrologiia na rubezhe vekov.

The peculiarities of the investigation of cerebrovascular diseases in Institute of Neurology of Rus. Acad. Med. Sci. for the last 50 years on the background of world achievements in this field are outlined. The very term "angioneurology" arose in the process of researches development in Institute of Neurology. The thesis was postulated that the achievements in development of clinical angioneurology were mainly determined as well as will be determined in future by the progress in fundamental investigations in medicine, biology and neurosciences.

[The molecular genetic approach to the study of dominant spinocerebellar ataxias]. / Molekuliarno-geneticheskii podkhod v izuchenii dominantnykh spinotserebelliarnykh ataksii.

At least 5 different genes of autosomal dominant spinocerebellar ataxias (SCA) were revealed recently. Their discovery permitted to elaborate the most perfect classification of this heterogeneous group of diseases. In two forms of ataxias (SCA1 and SCA3) the mutations consist in the expansion of CAG-trinucleotides repetitions. The Russian population of patients with dominant SCA (13 families) was examined for the first time in terms of the evaluation of mutant gene carriers of SCA1 and SCA3. SCA1 was diagnosed in 5 families on the molecular level. The cerebellar ataxia, dysarthria as well as pyramidal symptoms comprised the basis of SCA1 clinical pattern. There were no SCA3 cases at DNA-testing. The perspectives of DNA-diagnosis of inherited ataxias were considered.

[The prevention of acute disorders of cerebral circulation: the theory and the reality]. / Profilaktika ostrykh narushenii mozgovogo krovoobrashcheniia: teoriia i real'nost'.

It would be valid to conduct prophylaxis of acute cerebrovascular disturbances (ACVD) in the context of state integral program of prophylaxis of the main noninfectious diseases. Its basic principles are: control of risk factors, integral approach and priority of populational strategy. The main medical directions of ACVD prophylaxis are: control of arterial hypertension and prevention of cardioembolic insult in patients with heart rhythm disorders. It is also possible to prevent repeated ACVD in patients with transitory ischemic attacks and minor insults. The best result is prognosed in combination of the state policy of providing the healthy mode of life of population and medical prophylaxis of ACVD in high risk groups.