Genetic mutations with dominating pyramidal tract damage:
1. Familial bilateral lesion of the corticospinal tract and ventral funiculus of the spinal cord. The first signs manifest usually by the limited movements of the lower limbs that usually do not extend to the upper part of the body.
- Familial amyotrophic lateral sclerosis (ALS) is conditioned by the hereditary damage of the motor neurons in the motor cortex of the brain and lateral columns of the spinal cord and atrophy of the body muscles. The diagnosis of the ALS is given according to strict criteria [7]. Sometimes, at a first glance, the patients seem not to meet these criteria but with the time they develop additional signs that confirm diagnosis. ALS is frequently confused with dementia. Contemporary methods of testing show that the ALS patients display not only motor, but also sensitive disorders and vegetative dysfunction, although clinically it might not be that obvious [8-9]. The ALS patients are distinguished by the clinical manifestations of the disease and by the type of onset. They can be subdivided into the subgroups depending on the localization of the initial clinical manifestations (bulbar, upper or lower limbs) and speed of progress. Gender of the subject also influences the localization of the ALS onset; females have bulbar disorder more frequently [6]. It is possible that different subtypes of ALS have different pathogenesis. One of the studies of the genomic disorders in ALS has shown that single nucleotide polymorphism (SNP) differs in the patients depending on their gender. It is important to understand the reasons for heterogeneity of ALS as the subtypes of the disease with different pathogenesis can interfere with the clinical trials. The immune response can be important and vary depending on the patients’ population leading to further heterogeneity.
There are a lot of signs of the inflammation in ALS. The studies of the ALS pathophysiology show the signs of inflammation in the brain tissue conditioned by the immune mechanisms. The ALS research show morphological evidence of the microglia activation [10-12]. Microglia is activated after the tissue damage; it includes change of the structure and expression of the cell surface receptors and is the part of the innate immune response [12]. Activation of the microglia in ALS is additionally demonstrated by the signal transducer and activator of transcription 3 (STAT3) in the tissue of the dead ALS patients [13]. The studies of the gene expression showed upregulation of the TLR4 signal genes in ALS patients, and the authors suppose that it points to chronic activation of the monocytes/macrophages. Contemporary technologies visualize inflammation in the neural tissue, while activation of microglia can be demonstrated by the PR11195 ligand binding with benzodiazepine receptor [14]. PET demonstrated microglial activation in ALS using this ligand [15]. It is still unclear if this change happens at an early stage of the disease or it is the reaction to the inflammation of the sites of degeneration. Anyway, the immune mechanisms play their role in the development of the sites of “ill-being” and permit viewing ALS as the immune-associated disease. The morphological tests in the site of the disintegration of the motor neurons show accumulations of macrophages and T cells, and primarily, CD4+, CD8+, CD11a as well as the components of C3d and C4d compliment that can speak of active inflammatory reactions that are similar to those observed in lupus erythematosus [16-18]. There is evidence about immunoglobulins and immune complexes accumulation in the central nervous system in ALS [19].
