Use of botulinum toxin in children with cerebral palsy

Cerebral palsy in children is a syndrome of disorders resulting from damage to the central nervous system in its early development [1]. Damage to the structure of the upper motor neuron during its early development leads to dysfunction of the central motor control system and, consequently, to impairment of the child’s functional development [2,3]. The consequences of damage to the central motor control system include the presence of muscular tension disorders, especially spasticity [4,5]. Botulinum toxin is one of the many pharmacological agents used to reduce spasticity. Botulinum toxin therapy is one of the most effective and currently safest methods for the treatment of spasticity in children [6]

Muscle Spasticity and Its Interaction with Myofascial System of Children with Central Paresis

Traditionally, the problem of muscle spasticity was considered by experts as a kind of local problem associated with the inhibition or traumatisation of the central motor neuron in a certain part of its path. According to this approach, only the first stage of the causal relationship of the two systems was reflected: the nervous and the muscular systems. In the following, intrasystem relations of the muscle and muscle complex appeared according to the type of harmonization or destructivization of the activity of this system. To resolve this problematic situation, the article examines the original theory of Thomas V. Myers about “anatomical trains” or “myofascial meridians” as an integral musculoskeletal system of the human body, which forms the basis of its anatomy and motor activity. Key ideas of tensegrity as a structure of balanced compression-tension of the musculoskeletal system are identified, and it is necessary to rush to the targets, carrying out the correction of motor disorders of the tender age children with paresis of central type by means of physical education. For deeper understanding of the activities of these mechanisms of children myofascial status harmonization, the main myofascial lines were briefly characterized: surface back line, surface frontal line, lateral line, spiral line, arm lines. On this basis, working hypothesis was formulated as for using the holistic myofascial system capabilities of the child's body to correct both the tonic state of individual spastic muscles and to improve the general children motor status. To check the formulated hypothesis, the directions of the implementation of correctively directed physical education of tender age children with central paresis of different localization levels were indicated. An attempt was made to use the basic knowledge of the myofascial meridians functioning to increase the efficiency of diagnosing the state of musculoskeletal formations of children with spastic paresis, developing strategies and tactics for correcting their tonic state, methods and techniques for adjusting the balance of compression and tension of these structures to improve children motor activity and to improve the efficiency of their basic motor regimes mastering. There was made a fundamental conclusion that the correctional work by means of physical education should be preceded by preparatory work aimed at normalization of the whole myofascial system of a child with a spastic type of movement disorders, which can be carried out using purely medical techniques and the techniques based on the means of children physical education. Prospects of the scientific and practical development of the problem indicated in this article are highlighted separately

Therapeutic use of cerebellar transcranial theta burst magnetic stimulation in movement disorders. Mechanisms of action and biomarkers of efficacy

Movement disorders of different aetiology are characterized by an impairment in several interconnected areas of the motor system. Among the non-pharmacological options to improve motor symptoms, repetitive Transcranial Magnetic Stimulation (rTMS), represent a promising therapeutic tool due to its ability to induce long-term modulation of synaptic plasticity and its low incidence of side effects. Theta burst stimulation (TBS), a patterned protocol of rTMS, is able to induce long lasting excitatory (intermittent TBS) and inhibitory (continuous TBS) effects on cortical excitability and its very tolerable for patients due to its short duration. The high variability of response to TBS limits its use in clinical practice, thus research is focused on the characterization of predictors of response and biomarkers of efficacy. Among these, a common polymorphism of Brain Derived neurotrophic Factor (BDNF) gene, val66met, may influence the onset and progression of several neurodegenerative disorders and may alter the response to different TMS protocols, in particular TBS, but results are conflicting. Cerebellum is considered an interesting area of stimulation for rTMS protocols in movement disorders due to its ability to influence motor learning and control through its connections with all the areas of the motor system and its role in sensory-motor integration. Indeed, it is currently used as a target for neuromodulation in movement disorders involving different pathological mechanisms. The aim of the present study was to test the efficacy of inhibitory and excitatory cerebellar TBS in three movement disorders with different aetiology and to search possible biomarkers influencing its therapeutic effect. In the first project a single session of cerebellar continuous TBS (cTBS) was able to reduce levodopa-induced Dyskinesia in patients affected by Parkinson’s Disease (PD) and this effect was accompanied by a decrease in serum BDNF levels. Moreover, the presence of the Val66Met polymorphism of the BDNF gene was associated with a better response. In the second project 15 sessions of cerebellar intermittent TBS (iTBS) were able to improve motor symptoms in patients affected by Multiple system atrophy (MSA). No variations in serum BDNF levels after iTBS treatment were observed and apparently Val66Met polymorphism did not influence the clinical response. In the third project the excitability of primary motor cortex (M1) was increased by a single session of cerebellar iTBS in patients affected by Spino-Cerebellar ataxia 38 (SCA 38), an inherited disease characterized by mutation in the EVLOV-5 gene. iTBS was then applied for 10 sessions to the cerebellum of patients leading to an improvement of motor symptoms, especially postural stability. The Val66Met polymorphism did not influence the clinical response and the changes in motor cortex excitability. Overall, these data provide evidence for the use of cerebellar TBS in movement disorders; moreover, they suggest that BDNF Val66Met polymorphism may influence response to TBS but results vary depending on experimental model. Finally, they underline that measures of cortical excitability may provide information about the responsivity of the motor network to neuromodulation and may help to select an appropriate therapeutic protocol. Future studies will help to select other genetic, neurophysiological and imaging biomarkers leading to a better prediction and characterization of the clinical response to TBS

Automated, high accuracy classification of Parkinsonian disorders: a pattern recognition approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process

Progress in neuro-otology research in the last year

Herein, we summarize articles in the field of neuro-otology published in the Journal of Neurology over the last year. Topics included acute and chronic vertigo as well as auditory and ocular motor disorders. Characteristic lesion locations in Pusher syndrome are reported and the usefulness of bedside ocular motor tests in vertebrobasilar stroke is revisited. Probing the vestibular system and its value in predicting the outcome in vegetative state is discussed. Several articles address new diagnostic and therapeutic approaches in different disorders associated with chronic vestibular, auditory or gait deficits. In a series of case reports, we focus on different eye movement disorders in the vertical plane, which are often difficult to asses

The Cerebellar Dopaminergic System

In the central nervous system (CNS), dopamine (DA) is involved in motor and cognitive functions. Although the cerebellum is not been considered an elective dopaminergic region, studies attributed to it a critical role in dopamine deficit-related neurological and psychiatric disorders [e.g., Parkinson's disease (PD) and schizophrenia (SCZ)]. Data on the cerebellar dopaminergic neuronal system are still lacking. Nevertheless, biochemical studies detected in the mammalians cerebellum high dopamine levels, while chemical neuroanatomy studies revealed the presence of midbrain dopaminergic afferents to the cerebellum as well as wide distribution of the dopaminergic receptor subtypes (DRD1-DRD5). The present review summarizes the data on the cerebellar dopaminergic system including its involvement in associative and projective circuits. Furthermore, this study also briefly discusses the role of the cerebellar dopaminergic system in some neurologic and psychiatric disorders and suggests its potential involvement as a target in pharmacologic and non-pharmacologic treatments

The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases

To the question of correction of Parkinson's disease by means of physical therapy

Topicality. Determining the level of effectiveness of the use of physical therapy in the early stages of Parkinson's disease to stop the rate of its progression.Objectives of the study: to develop and apply to patients with Parkinson's disease in the early stages with predominantly non-motor manifestations physical therapy program. To study the effectiveness of the developed physical therapy program on the scale of assessment of the state of non-motor symptoms, mental disorders and cognitive impairment in Parkinson's disease.Research results. After the physical therapy, the patients' condition improved significantly. Cognitive, mental functions, motor abilities and manifestations from the side of the cardiovascular system are effectively improved with the help of physical exercises and the whole complex of physical therapy we have developed. Changes in the status of patients after physical therapy for the better were recorded by both subjective and objective survey data. Particularly significant were the data from the study on the scale of assessment of patients with non-motor manifestations of Parkinson's disease (scale of non-motor symptoms – NMSS, scale of mental disorders – MMSE, Montreal scale of cognitive disorders-MOCA). They showed a significant statistically significant difference between the control and the main group of patients towards improvement in the final examination.Conclusions. According to research data, the condition of patients who received the physical therapy complex was significantly better than in the group of patients who did not receive physical therapy, indicates the effectiveness of the developed and used complex physical therapy for non-motor manifestations of Parkinson's disease and allows us to recommend it for widespread use

Loss of Specificity in Basal Ganglia Related Movement Disorders

The basal ganglia (BG) are a group of interconnected nuclei which play a pivotal part in limbic, associative, and motor functions. This role is mirrored by the wide range of motor and behavioral abnormalities directly resulting from dysfunction of the BG. Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events. In the normal BG, this modulation is highly specific, with each neuron related only to a small subset of behavioral events depending on specific combinations of movement parameters and context. In many pathological conditions involving BG dysfunction and motor abnormalities, this neuronal specificity is lost. Loss of specificity (LOS) manifests in neuronal activity related to a larger spectrum of events and consequently a large overlap of movement-related activation patterns between different neurons. We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG. The prevalence of LOS in a many BG-related disorders suggests that neuronal specificity may represent a key feature of normal information processing in the BG system. Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control

EARLY ASSESSMENT OF THE RISK OF DYSLEXIA AND DYSGRAPHIA AMONG CHILDREN AGED 5-6 IN THE ASPECT OF EDUCATIONAL AND THERAPEUTIC WORK OF KINDERGARTENS

Reading and writing are basic skills that guarantee child’s learning. Therefore, it is important that the child has mastered these skills to the best extent. Unfortunately, not all children can meet the requirements in the field of learning to read and write. Problems of varying intensity and range appear, they are caused by various disorders of the perceptual-motor functions. Children who may have problems with reading and writing in the future can already be seen in the kindergarten. Therefore, the aim of the study was to diagnose the risk of dyslexia and dysgraphia among children aged 5-6. The study included 300 children from kindergartens in Biała Podlaska, Poland. The results of the study showed that children at risk for dyslexia and dysgraphia are present in the study group. The most frequent manifestations of these disorders were in the field of fine motor skills, gross motor skills, language functions, visual functions and attention. They were caused by various factors related to the functioning of the nervous system that affect its development. Among the children diagnosed with these disorders, therapeutic measures have been taken to help reduce developmental delays and make it easier for them to learn in primary school