ARIPIPRAZOLE INDUCED ACUTE SEVERE EXTRAPYRAMIDAL TRACT SYMPTOMS

The advent of novel atypical Antipsychotics called second generation antipsychotics (SGA) namely, quetiapine, olanzapine, Clozapine, this major problem of disturbing Extrapyramidal system [EPS] was blocked to a larger extent. Among the next Generation antipsychotics, Aripiprazole is reported to be a good safety prole antipsychotic because of its special and unique mechanism of action. Various studies have shown the incidence of EPS with this antipsychotic to be very much Insignicant. Therefore there has been increased use of aripiprazole due to its reported safety prole over time. We report a case of Acute severe Extrapyramidal Tract Symptoms induced by the use of Aripirazole which showed dramatic improvement following treatment discontinuation and hereby suggest that the disorder should be considered a possible adverse affect of aripiprazole to make more balanced treatment choices

Toxic Models of Parkinson's Disease: History and Prospects

The review article presents data on the history of research of extrapyramidal system dysfunctions, modern ideas about the etiology and diagnosis of Parkinson's disease, as the most common disease of the group of extrapyramidal disorders. Currently, no concept of effective therapy for patients with extrapyramidal system dysfunction has been developed, but it has been proven that the probability of developing the disease largely depends on the genetic predisposition and the level of environmental pollution. In the early stages, the disease is slow and asymptomatic, but gradually more than half of patients with Parkinson's disease die, and others need outside care. According to experts, in the near future, Parkinson's disease will become a problem for a significant part of people, because today it affects more and more people of working age. Under such conditions, reliable and early diagnosis of the disease is of great importance, which guarantees timely and most effective treatment. Modern therapies fail to stop the progressive death of the dopaminergic neurons of the substantia nigra, but traditional treatment can achieve symptomatic relief. Currently, it is known that the probability of developing Parkinson's disease depends on the genetic predisposition and the level of man-made environmental stress. The researchers consider that the pathological development of Parkinson's disease in the brain begins in the lower structures of the brain stem with the involvement of the caudal-Rostral nuclei, as well as the involvement of the cortico-basal ganglia-cerebellar pathways. The pathological process affects the ascending pathways and gradually passes to the midbrain, directly to the black substance, spreads from there and weakens the mesocortex and neocortex. Injuries in the brain stem lead to disorganization of the cortico-basal ganglia and cerebellar pathways, followed by the formation of alternative pathways to compensate for the initial disorders in the early stages of the disease. In addition, in Parkinson's disease, intracellular Lewy bodies and neurites formed by the protein alpha-synuclein are created, which are found in the autopsy material of most patients. Poor results of diagnostic evaluation and treatment of Parkinson's disease are usually associated with a lack of understanding of the pathogenesis of Parkinson's disease. The study of the biological basis and pathogenesis of Parkinson's disease is an important task of a whole complex of scientific studies of extrapyramidal system dysfunction. Conclusion. The article discusses the creation of toxic models of Parkinson's disease in vivo and in vitro, which help to recreate the pathogenesis of the disease for early diagnosis and the development of new ways to treat neurodegenerative diseases. In toxic models of Parkinsonism, not only deficits of motor functions such as bradykinesia, tremor, and posture disorders are actively studied, but also non-motor symptoms such as sleep disorders, neuropsychiatric and cognitive abnormalities

NEUROPSYCHOLOGICAL PRINCIPLES OF COGNITIVE AND COMMUNICATIVE ACTIVITIES DIAGNOSIS IN ADULTS WITH EXTRAPYRAMIDAL SYSTEM DISORDERS

The aim is to determine the neuropsychological peculiarities of cognitive and communicative activities in adults with the extrapyramidal system disorders. Materials and methods: The research was conducted during 2018-2021, during which a retrospective analysis of medical treatment records of the patients with extrapyramidal disorders of various etiologies was performed. The research involved 137 adult patients with extrapyramidal disorders: 93 persons with Parkinson’s disease, 36 people with manganese encephalopathy, 5 persons with progressive supranuclear palsy and 3 people with Wilson-Konovalov disease. Results: A significant difference between the indicators of preservation of cognitive and communicative activities and the communicative and semantic component in the group of patients with Parkinson’s disease without speech disorders and Parkinson’s disease and between the groups of patients with Parkinson’s disease without speech disorders and progressive supranuclear palsy indicates the need for experimental correctional and rehabilitation work to restore cognitive and communicative activities of the patients with extrapyramidal disorders. Conclusions: The most preserved communicative and speech function was found in the patients who had initial and mild stages of the disease, in particular in the patients with Parkinson’s disease without speech disorders. It should be emphasized that the diagnosis of cognitive and communicative activities and the communicative and semantic component in adults with extrapyramidal disorders is a necessary prerequisite for the organization of the process of comprehensive rehabilitation treatment.

Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study

Purpose Recent evidences have suggested the possible presence of an involvement of the extrapyramidal system in Fabry disease (FD), a rare X-linked lysosomal storage disorder. We aimed to investigate the microstructural integrity of the main tracts of the cortico-striatal-thalamo-cortical loop in FD patients. Methods Forty-seven FD patients (mean age = 42.3 ± 16.3 years, M/F = 28/21) and 49 healthy controls (mean age = 42.3 ± 13.1 years, M/F = 19/28) were enrolled in this study. Fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) maps were computed for each subject, and connectomes were built using a standard atlas. Diffusion metrics and connectomes were then combined to carry on a diffusion MRI tractometry analysis. The main afferent and efferent pathways of the cortico-striatal-thalamo-cortical loop (namely, bundles connecting the precentral gyrus (PreCG) with the striatum and the thalamus) were evaluated. Results We found the presence of a microstructural involvement of cortico-striatal-thalamo-cortical loop in FD patients, predominantly affecting the left side. In particular, we found significant lower mean FA values of the left cortico-striatal fibers (p = 0.001), coupled to higher MD (p = 0.001) and RD (p < 0.001) values, as well as higher MD (p = 0.01) and RD (p = 0.01) values at the level of the thalamo-cortical fibers. Conclusion We confirmed the presence of an alteration of the extrapyramidal system in FD patients, in line with recent evidences suggesting the presence of brain changes as a possible reflection of the subtle motor symptoms present in this condition. Our results suggest that, along with functional changes, microstructural damage of this pathway is also present in FD patients.

Diagnostic capabilities of posturological methods in extrapyramidal disorders

The posture is the position of the body in space, the ultimate goal of which is to maintain balance in static and dynamic conditions. The balance of the body is due to a complex system of regulation. The field of knowledge that studies balance maintenance processes is posturology. For over 20 years, stabilometry as a method of diagnosing postural balance has been widely used in clinical practice. This method has found its application in patients with pathologies of central and peripheral nervous systems. In this review we present modern concepts of postural balance formation and mechanisms of postural balance maintenance, as well as diagnostic capabilities of stabilometry in patients with diseases of extrapyramidal system.

Comparison of Mono-dopaminergic and Multi-target Pharmacotherapies in Primary Parkinson Syndrome and Assessment Tools to Evaluate Motor and Non-motor Symptoms

Background:Primary Parkinson syndrome is mostly treated by dopaminergic drugs, while the progression of the disease is not altered. Some non-dopaminergic are available, which are administered only after the Parkinsonian symptoms get worse.Objective:The objective of this review is to give basic results in order to compare a dopaminergic and non-dopaminergic pharmacotherapy in Parkinson’s disease and to control whether the add-on pharmacotherapy with non-dopaminergic drugs can inhibit the progression of the disease.Methods:In primary Parkinson syndrome, the altered activity of classical neurotransmitters and neuropeptides in the extrapyramidal system is summarized and up-dated. Anatomical studies on neural networks in the basal ganglia are mentioned. The direct, motor facilitatory pathway (D1 dopaminergic neurons) from the substantia nigra to the thalamus, via the internal globus pallidus, and the indirect, motor inhibitory pathway via D2 dopaminergic neurons have been considered. These established anatomical pathways have been brought in line with the neural interactions derived from neurotransmitter balances or imbalances. Besides, preclinical and clinical studies of effective non-dopaminergic anti-Parkinsonian drugs are reviewed.Results:It can be hypothesized that glutamatergic neurons enhance dopamine deficiency in the substantia nigra and putamen through an increased presynaptic inhibition mediated by NMDA receptors. In the putamen, 5-HT2A serotonergic neurons counteract D2 dopaminergic neurons and A2A adenosine neurons antagonize D2 dopaminergic neurons by activating glutamatergic neurons, which presynaptically inhibit via subtype 5 of metabotropic glutamatergic receptors, D2 dopaminergic neurons. In the extrapyramidal system, an up-dated neural network, which harmonizes established anatomical pathways with derived neural interactions, is presented. In Parkinson’s disease, a question should be answered, whether a combination of dopaminergic and non-dopaminergic drugs can promote an increased motor and non-motor functioning.Conclusion:A mono-target pharmacotherapy (using only dopaminergic drugs) and a multi-target pharmacotherapy (i.e. by combining dopaminergic and non-dopaminergic drugs) are compared. The alternate administration of dopaminergic and non-dopaminergic anti-Parkinsonian drugs, administered at different times during the day, must be tested in order to inhibit the progression of the disease. Assessment tools can be used to evaluate motor and cognitive functions. Moreover, imaging examination techniques can be also applied to control the course of the disease.