Герпетический энцефалит, клиника, современные методы диагностики, терапия

Relevance: The problem of Alzheimer's disease (AD) in spite of a long period of study, now is still relevant, because etiopathogenesis and therapy are not clear so far.

Aim: To analyze a modern level of diagnostics and therapy of Alzheimer's disease based on the corresponding literature sources.

The results. Currently, in addition to the criteria of ICD-10 for diagnostics of Alzheimer's disease the criteria of NINCDS–ADRDA (The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association) are widely used proposed by cognominal research institutions in 1984 year. According to the given criteria 4 degrees of reliability of clinical diagnosis are marked:

1. Clinically accurate diagnosis is characterized by alleged criteria of diagnosis and implies a histological confirmation of illness resulting from performing a biopsy or autopsy.

2. The anticipated diagnosis is characterized by clinically and neuropsychologically confirmed dementia, advance, at least two disorders of cognitive functions, the beginning of the disease between the ages of 40 to 90 years and the absence of other diseases that could lead to the development of this syndrome.

3. The likely diagnosis is considered in cases of advance of dementia, but atypical onset and lack of other alleged causes.

4. Unlikely diagnosis is when a patient is detected either symptoms of localized brain lesions or ekstrapiramidnye disorders, or sudden onset of disease is established out of anamnesis.

The authors of the NINCDS-ADRDA criteria allocated 8 cognitive functions, which can be violated in Alzheimer's disease: memory, speech, perception, attention, ability to create, orientation, ability to decide and the ability to perform any work/task. On a par with NINCDS-ADRDA the criteria by the DSM (Diagnostic and Statistical Manual of Mental Disorders) are used first published by the American Psychiatric Association in the year 1952. Since then, the DSM has been repeatedly revised. Currently, the DSM-IV criteria are used [6]. According to the fourth edition of the DSM gradually raised and progrediently increasing violation of memory, are necessarily observed in Alzheimer's disease , as well as violation of at least one of the following cognitive functions: speech, praxis, gnosis and executive functions. Patients should not be a breach of the level of consciousness and other signs of neurological or somatic diseases that may lead to cognitive disorders.

Radiological diagnostic methods. Singularity of Alzheimer's disease is primary involvement of temporopariental cerebral hemispheres of brain and cholinergic neurons of the Meynert basal nidus. Primarily, the medial temporal lobe divisions are damaged in Alzheimer's disease. Atrophy of the hippocampus is an early, although not absolutely specific marker of the disease. Single small vascular local areas or limited periventricular leukoaraiosis does not exclude the diagnosis of Alzheimer's disease [8].

An important neuropatological pecularity of the of Alzheimer's disease are the β-amyloidal protein sediments. New advances in positron-mission tomography show β-amyloid in the brain [1].

Currently, medications of several pharmaceutical groups are used in Alzheimer's disease:

1. Central inhibitors of acetyl cholinesterase (amiridin, donepezil, galantamine)

2. Antagonists of NMDA - receptors (memantine).

3. There are indications to the ability to slow down the advance of the disease by the replacement therapy with the use of estrogens in postmenopausal women period, non-steroidal anti-inflammatory medications, vitamin E and selegilin [5].

It is also expected that, in addition to the acetyl cholinesterase level regulation of acetylcholine in the brain is carried out by another enzyme - butyrylholinesterase[6]. Therefore, you should expect more effect from medications with dual action (rivastigmine) i.e. able to inhibit and acetyl holinesterase, and butyrylholinesterase.

Pathogenesis of BA currently is not fully understood, but according to many scholars it is based on neurodegeneration, so it would be logical to assume the effectiveness of neurotropic therapy, however application of the neurotrophic factors is hampered by their large variety and multifunctionality. Neurotrophic activity of cerebrolysin was confirmed in a number of studies [7-10]. This medication is used for the treatment of dementias of different genesis and stroke in our country and abroad for more than 40 years [2-3]. The data demonstrating the effectiveness of courses of a four- week [3] and extended a two-year course of therapy with the use of cerebrolysin in Alzheimer's disease were published in the year of 2007 [3-4].

There is evidence of significant role of oxidative stress in the pathogenesis of Alzheimer's disease. Proteins and lipids, as well as DNA are subjected to oxidation in this disease[5]. There is a theory that the root cause of the extracellular accumulation of substrates is their peroxide oxidation [6]. Scientists made repeated attempts to affect this link of the pathogenesis of the disease. For the time being, it has been proven that the use of vitamins with antioxidant activity, reduces the risk of developing Alzheimer's disease [7]. A link between the intensity of lipid peroxidation and clinical picture of Alzheimer's disease has been set up. Some effects of medication-antiholinesterase inhibitors may be associated with effects on the lipid peroxidation of membranes.

A domestic antioxidant medication that has gained a reputation in many other pathologies is Mexidol. Mexidol ® - is an antioxidant and antihypoxant of direct energizing action, which determines its mechanism and spectrum of pharmacological effects. It is an inhibitor of the free-radical processes of lipid peroxidation, activates superoxidedismutase, has an impact on the physicochemical properties of the membrane , increases the content of polar fractions of lipids in membrane, activates energy synthesizing mitochondrial functions and improves energy metabolism in the cell and thus protects the unit of the cell and structure of their membranes. Thus, the mechanism of action of Mexidol is defined particularly by its antioxidant properties, ability to stabilize the biomembrane cells , to activate the energy synthesizing function of mitochondria, to modulate receptor complexes work and passage of ionic currents, to strengthen the binding of endogenous substances, to improve synoptic transfer and interaction of brain structures.

Thanks to this mechanism of action, Mexidol affects key reference links in the pathogenesis of various diseases, has a large range of effects. A significant advantage of Mexidol is that it has minor side effects and low toxicity. The medication has a high bioaccessibility.It can be used intravenously (by stream or drop infusion), intramuscularly and inside, which makes it a more convenient and affordable for patients in an outpatient setting. The medication is combined with almost all drugs, which is very important for patients with Alzheimer's disease usually somatic burdened. Mexidol also affects the accompanying cerebrovascular cause of dementia, which improves mnestic processes, and enhances the quality of life for this group of patients.

There is evidence that for the time being medications are being developed, which will directly affect the primary problem of Alzheimer's disease – the process of concentration of amyloids. We are talking about the so-called antiamyloidal therapy. Antiamyloidal therapy is based on the introduction of antibodies that inhibit the synthesis of amyloid or lead to its destruction. It can be both antibodies directly to amyloid [1, 5, 6, 11], and antibodies to enzymes involved in its synthesis [3]. In a preliminary clinical trial the positive effects of intravenous injection of purified donor immunoglobulin was shown [8]. It should be stressed, however, that attempts to treat the disease with the help of immunoglobulins associated with high risk for severe complications of allergic origin.

Conclusions: This study found out that cognitive disorders leading to social maladjustment among patients with Alzheimer's disease are associated not so much with diffuse cerebral atrophy, but with more local atrophy of the temporal lobes and the hippocampus. Increase in the expressivity of leukoaraiosis is accompanied by clinically disturbed balance, according to MRT- greater expansion of the ventricles. Human postural functions in Alzheimer's disease are heavily influenced by age, wherein dynamic characteristics (walking) are also associated with the size of the ventricular system, and violations of the balance are associated with availability and incidence of periventricular leukoaraiosis. Application of the listed diagnostic criteria has enabled to improve the accuracy of clinical diagnostics of Alzheimer's disease up to 90-95%, however, a definite diagnosis can be made only when it is confirmed by the data of obductional neuromorphological brain research. The criteria also do not solve the issue of diagnostics at an early stage of the disease, since they become informative only with the development of cognitive impairment degree of dementia. The treatment of Alzheimer's disease currently used is most efficient at as the early stages of the disease. However, it is at the early stage that the diagnostics of Alzheimer's disease and other dementias is extremely difficult. In this connection, it should be noted that the ICD-10 does not fully reflect the course and staging development of Alzheimer's disease [4,11].

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