The crisis of contemporary neurology

Despite impressive academic achievements in the studies of the human brain and large-scale international projects aiming to uncover the mysteries of the human brain, no obvious breakthroughs and advances in the treatment of neurological diseases are observed by now. Neurology remains one of the most promising and rapidly developing fields of medicine and its borders have been considerably expanded into the areas of neuroengineering and neurotechnologies with the emergence of new technologies. However, facts are stubborn things and the scientific advances pale when compared with the facts.

According to the data of the World Health Organization (WHO) every third of the global population suffers from brain disorders. The neural-psychiatric diseases are observed in 15% of the population, which totals almost 450 million. In the past decade the number is said to grow by 40% due to children and teenagers.

The number of the patients with organic diseases of the brain grows exponentially, which is associated with the advances of neuro-resuscitation and intensive care: life support, management of medically induced coma, systemic thrombolysis and anaesthetic support to the vascular and traumatic neurological patients. The efforts of intensivists have led to the abrupt increase of the survived patients after severe brain injuries, strokes and intoxications with vast damages of the brain tissue and brain defect incompatible with productive intellectual life. The success of highly technological neurosurgery leads to the abrupt increase of the severe disability among those who survived the injury with pronounced organic and psychoorganic defects resulting in the chronic vegetative state, dementia and complete disablement.

Ageing of the population is also unavoidable and the number of age-related degenerative diseases keeps growing: by 2050 one of 85 individuals is expected to have Alzheimer’s disease, so that by 2050 the world will have 13.8 million cases of Alzheimer’s disease.

While the fundamental issues of neuroscience and neurology such as understanding of the brain and principles of brain functioning remain unsolved, it is impossible to find the way out of the technological dead-end in the development of computer technologies and artificial intelligence (AI) systems. We still have no clear understanding of the way our intellect is organized, or of the memory location. Recently, the progress of computation systems that we have been observing for part 50 years has faced a serious limitation, known as Power Wall. According to the Moore’s law the only way to enhance the capacity of computers is to increase the number of processors. However, this leads to increased energy consumption, entailing increase of net costs of all operation works. Expansion of the architecture of computers causes entropy increase due to high risks of separate components failure (Walker, 2012). Meanwhile, the human brain functions at minimal energy consumption. If we understood how our brain functions, the energy of one bulb would be enough for the work of a supercomputer.

In the past century the figures that might demonstrate the efficiency of the treatment of neurological and psychiatric diseases almost did not change, while the treatment expenses grew 200-fold. According to the Human Brain Project report (2012) the costs of the neural diseases therapy total 80 billion euro a year and keep growing.

What do we know about the fundamental genetic and epigenetic basis of the neural and psychiatric disorders?

• All neural disorders have personalized genetic substrate (innate or acquired genetic defect) in the neural cell (NC), which is conditioned by the formation and accumulation of the specific local transitory or permanent mutations in certain chromosomes of the nucleus of the damaged NC.
• The reason for structural (gene modification) and functional damage (gene expression disorder) of the genome lies in the pathological information effects on the NCs provided by the etiological factors of the diseases (stress, intoxication, infection, injury and others) or pathogenic interpersonalised interactions of the NCs microenvironment.
• Even if the NC has structural genetic and epigenetic damages, it can be quite resistant to the continuing etiological effect on it and remain able to adequately perform its specialized functions (compensation). Accumulation of the critical number of the mutations in the genome or pronounced dynamic epigenetic shifts lead to the instability of the genome: the disease manifests or decompensates.
• Clinical manifestations of specific neural disorder depend on the morphological phenotype of the damaged NC, which is conditioned by the changes in its proteome, metabolome and secretome.
• Altered proteome defines the phenotype o the damaged NC and manifests in its cytological, histological and histochemical characteristics. The metabolome and secretome of the damaged NC define its functional activity or the degree of its functional insufficiency.
• The changes of the proteome of the damaged NC are conditioned by the structural damages of the genome at the chromosome level (damaged or reconstructed DNA, iRNA), and by the epigenetic changes at the level of transcriptome represented by the disordered intrapersonalised and interpersonalised signaling.
• Instability of the NC genome underlies the basic pathogenetic mechanisms of the tumor, genetic and degenerative diseases of the brin an spinal cord; it manifests by the NC transcriptome disorder and changes in the gene expression profile.

Our team has also made its contribution to the understanding of the human brain organization and presented the views and ideas about the theoretical and practical aspects of neurology that have been stated in over 120 articles and books. If you are interested, we strongly recommend you to read them.