scholarly journals Dystonia in children

2021 ◽  
Vol 24 (2) ◽  
pp. 112-121
Author(s):  
A. A. Lyalina ◽  
L. A. Pak ◽  
A. P. Fisenko ◽  
O. B. Kondakova ◽  
I. E. Smirnov
Keyword(s):  
Botulinum Toxin ◽  
Treatment Options ◽  
Pathological Process ◽  
Motor Disorder ◽  
First Choice ◽  
Generalized Dystonia ◽  
Primary Dystonia ◽  
The Central Nervous System ◽  
Muscle Groups ◽  
Diagnostic Work

Dystonia is a motor disorder characterized by sustained muscle contractions producing twisting, repetitive, and patterned movements or abnormal postures. Dystonia is among the most commonly observed motor disorders in clinical practice in children. Unlike dystonia in adults that typically remains focal or spreads only to nearby muscle groups, childhood dystonia often generalizes. Classification of dystonia has direct implications for narrowing down the differential diagnosis, choosing the diagnostic work-up, predicting the prognosis, and choosing treatment options. The etiology of pediatric dystonia is quite heterogeneous. The etiological classification distinguishes primary dystonia with no identifiable exogenous cause or evidence of neurodegeneration and secondary syndromes. Dystonia can be secondary to any pathological process that affects the basal ganglia. The treatment options of childhood dystonia include several oral pharmaceutical agents, botulinum toxin injections, and deep brain stimulation therapy. Botulinum toxin treatment is the first choice treatment for most types of focal dystonia. In children it is less used because dystonic forms are mainly generalized, but it might also be helpful in controlling the most disabling symptoms of segmental or generalized dystonia. Long-term electrical stimulation of the globus pallidum internum is now established as an effective treatment for various types of movement disorders including dystonia. However, this method has not yet found its application in Russia due to the difficulty of implementation and the lack of patient routing. To increase the effectiveness of complex therapy of dystonia in children, new pathogenetic methods of treatment of common forms of primary dystonia and dystonic syndromes in the structure of degenerative diseases of the central nervous system are needed, as well as the development of optimal algorithms for the diagnosis and treatment of these patients.

scholarly journals Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1548
Author(s):  
Mustafa N. Mithaiwala ◽  
Danielle Santana-Coelho ◽  
Grace A. Porter ◽  
Jason C. O’Connor
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Kynurenine Pathway ◽  
Economic Problem ◽  
Cns Disease ◽  
Therapeutic Implications ◽  
Efficacious Treatment ◽  
The Central Nervous System ◽  
Significant Health

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

scholarly journals Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

2021 ◽  
Vol 22 (14) ◽  
pp. 7536
Author(s):  
Inez Wens ◽  
Ibo Janssens ◽  
Judith Derdelinckx ◽  
Megha Meena ◽  
Barbara Willekens ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Treatment Options ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Tailored Treatment ◽  
Key Issues ◽  
The Central Nervous System

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.

A Systematic Review of the Omohyoid Muscle Syndrome (OMS): Clinical Presentation, Diagnosis, and Treatment Options

2021 ◽  
pp. 000348942199503
Author(s):  
Jerome Zhiyi Ong ◽  
Alex Chengyao Tham ◽  
Jian Li Tan
Keyword(s):  
Systematic Review ◽  
Botulinum Toxin ◽  
Traumatic Event ◽  
Botulinum Toxin Injection ◽  
Treatment Options ◽  
Neck Mass ◽  
Good Prognosis ◽  
Common Symptom ◽  
Management Options ◽  
Omohyoid Muscle

Objective: Omohyoid muscle syndrome (OMS) is a condition that causes a X-shaped lateral neck lump on swallowing, caused by the failure of the central tendon of the omohyoid muscle to restrict movement of the muscle during swallowing. We aim to review the etiology, pathophysiology, diagnostic tests, and management options for this condition. Data Sources: Pubmed, MEDLINE, EMBASE, and Cochrane databases were searched for all articles and abstracts related to OMS up to 29th July 2020. Review Methods: A systematic review was performed, data extracted from relevant full text articles. Both quantitative data and qualitative data were analyzed. Results: Twenty cases of OMS were reported. Patients presented at a mean age of 36.0. All cases were Asian. There is a 7:3 ratio of males to females. The most common symptom was a transient neck mass. Most cases were managed conservatively with good prognosis. Open or endoscopic transection of the muscle and ultrasound-guided botulinum toxin injection were 3 treatment options, with no recurrence at 4 years, 6 months, and 6 months respectively. Conclusion: OMS could be genetic as all cases were Asian in ethnicity. The deep cervical fascia which usually envelopes the omohyoid muscle may be weakened by stress as 20% of cases had a preceding traumatic event. Real-time ultrasonography establishes the diagnosis, demonstrating the anterolateral displacement of the sternocleidomastoid muscle by a thickened omohyoid muscle during swallowing. Surgical transection can achieve cure, but due to limited studies available, they should be reserved for patients who are extremely bothered. Intramuscular injection of botulinum toxin is an effective alternative, but recurrence is expected.

scholarly journals In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

2021 ◽  
Author(s):  
Antonio Munafò ◽  
Stefano Frara ◽  
Norberto Perico ◽  
Rosaria Di Mauro ◽  
Monica Cortinovis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Public Health Problem ◽  
Cardiovascular Death ◽  
Regulation Of Transcription ◽  
Major Public Health Problem ◽  
Obese Patients ◽  
Ephedra Sinica ◽  
The Central Nervous System ◽  
Treatment Of Obesity

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

scholarly journals Components of a Response Programme Involving Inhibitory and Excitatory Reflexes in the Surf Clam

1970 ◽  
Vol 53 (3) ◽  
pp. 711-725
Author(s):  
DEFOREST MELLON ◽  
DAVID J. PRIOR
Keyword(s):  
Ganglion Cells ◽  
Adductor Muscle ◽  
Type I ◽  
Surf Clam ◽  
Response Characteristics ◽  
Sensory Pathways ◽  
Intact Muscle ◽  
Input Organization ◽  
The Central Nervous System ◽  
Muscle Groups

1. Electrical records from ganglion cells in the central nervous system and from intact muscle groups controlling siphon retraction and shell-valve adduction have revealed qualitative similarities in the response characteristics of two neurone-effector systems following stimulation of tactile afferents. 2. Simultaneous electrical records from neurones and muscle indicate that Type I ganglion cells are motoneurones to the fast portion of the posterior adductor muscle. 3. The waveform and polarity of the post-synaptic responses of Type 1 cells depend critically upon the intensity of stimulation over intact sensory pathways. High-intensity input transiently excites the fast portion of the adductor; low-intensity input inhibits the adductor motoneurones. The input organization of Type I neurones therefore permits discrimination of stimulus magnitude and thus controls the characteristics of the response programme.

scholarly journals Development of a technique for DNA detection and identification of toxigenic strains of Clostridium botulinum types A, B, E by the Real-Time PCR method

2018 ◽  
Vol 2 (4) ◽  
pp. 36-43
Keyword(s):  
Botulinum Toxin ◽  
Real Time ◽  
Clostridium Botulinum ◽  
Specific Activity ◽  
Food Samples ◽  
Analytical Sensitivity ◽  
Detection And Identification ◽  
The Central Nervous System ◽  
Toxigenic Strains ◽  
Definition Of

Botulism is dangerous toxic infection caused by a toxin produced by the bacterium Clostridium botulinum. The mortality rate from botulism can reach 70% of all cases of illness in case of untimely initiation of treatment. The pathogenesis of botulism involves the damage to the central nervous system by a toxin produced by C. botulinum. Currently there are seven recognized antigenic types of this toxin. Botulinum toxin is included into the group of biological agents and it is one of the most likely agents to be used in a biological attack. Since botulinum neurotoxin is a complex nucleoprotein complex and the traces of DNA can be detected even in purified toxin preparations, we have elaborated a technique for detecting and identifying DNA of toxigenic strains of Clostridium botulinum types A, B, E, that cause human botulism in most cases. This technique is based on the the detection of residual amounts of this DNA in botulinum toxin using multiplex real-time polymerase chain reaction (PCR) assay with fluorescent hybridization detection. The main obstacle to development of a technique for the detection and identification of DNA of toxigenic strains is the high variability of the genes responsible for the synthesis of botulinum toxin. We have established a region of the gene with the lowest homology in all strains. This requirement is met by a fragment of the bont gene that encodes a light chain of a neurotoxin and is highly conserved in the strains of C. botulinum producing one type of toxin. The paper represents the results of the definition of analytical sensitivity and specific activity of the developed method. The specificity of the determination is 100%, the analytical sensitivity – 1×10 2 mc./ml. The method can be used to analyze food, samples of clinical materials and environmental samples suspected of being contaminated with toxigenic strains of C. botulinum

scholarly journals USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Liu ◽  
Qingbai Liu ◽  
Bin Yan ◽  
Ziqiang Zhu ◽  
Yaozeng Xu
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
Pathological Process ◽  
Joint Disease ◽  
Matrix Remodeling ◽  
Ros Production ◽  
Caspase 1 ◽  
Enhanced Production

Osteoarthritis (OA), the most common form of arthritis, is a very common joint disease that often affects middle-aged to elderly people. However, current treatment options for OA are predominantly palliative. Thus, understanding its pathological process and exploring its potential therapeutic approaches are of great importance. Rat chondrocytes were isolated and exposed to hydrogen peroxide (H2O2) to mimic OA. The effects of H2O2 on ubiquitin-specific protease 7 (USP7) expression, reactive oxygen species (ROS) levels, proliferation, inflammatory cytokine release, and pyroptosis were measured. USP7 was knocked down (KD) or overexpressed to investigate the role of USP7 in OA. Co-immunoprecipitation (Co-IP) was used to study the interaction between USP7 and NAD(P)H oxidases (NOX)4 as well as NOX4 ubiquitination. NOX4 inhibitor was applied to study the involvement of NOX4 in USP7-mediated OA development. USP7 inhibitor was given to OA animals to further investigate the role of USP7 in OA in vivo. Moreover, H2O2 treatment significantly increased USP7 expression, enhanced ROS levels, and inhibited proliferation in rat chondrocytes. The overexpression of USP7 enhanced pyroptosis, ROS production, interleukin (IL)-1β and IL-18 levels, and the expression level of NLRP3, GSDMD-N, active caspase-1, pro-caspase-1, matrix metalloproteinases (MMP) 1, and MMP13, which was abolished by ROS inhibition. The USP7 KD protected rat chondrocytes against H2O2-induced injury. Co-IP results showed that USP7 interacted with NOX4, and USP7 KD enhanced NOX4 ubiquitinylation. The inhibition of NOX4 blocked the pro-OA effect of USP7. Moreover, the USP7 inhibitor given to OA animals suppressed OA in vivo. USP7 inhibited NOX4 ubiquitination for degradation which leads to elevated ROS production. ROS subsequently activates NLPR3 inflammasome, leading to enhanced production of IL-1β and IL-18, GSDMD-N-dependent pyroptosis, and extracellular matrix remodeling. Thus, UPS7 contributes to the progression of OA via NOX4/ROS/NLPR3 axis.

scholarly journals Heterogeneity of the mechanisms of action of antidepressants

2021 ◽  
pp. 11-17
Author(s):  
V. L. Kozlovskii ◽  
M. Yu. Popov ◽  
D. N. Kosterin ◽  
O. V. Lepik
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Response ◽  
Pathological Process ◽  
Clinical Activity ◽  
Clinical Effects ◽  
Drug Induced ◽  
Neuronal Interactions ◽  
Neurophysiological Studies ◽  
The Central Nervous System ◽  
Monoamine Receptors

The article discusses the heterogeneous mechanisms of the pharmacodynamics of antidepressants that underlie the therapeutic response. Sharing the similar clinical activity, antidepressants determine the development of drug-induced homeostasis by means of different molecular mechanisms (selective or nonselective blockade of monoamine reuptake, inhibition of monoamine oxidase, blockade of certain monoamine receptors). However, an increase of serotonin and other monoamines concentrations in the synapses of the central nervous system is only the initiating factor in the development of specific clinical effects. The latter are probably determined by other neurochemical effects, including changes in the density of postsynaptic receptors and an increase in the synthesis of neurotrophic factors. However, the primary mechanisms that increase monoamine concentrations in the synapses might not always “work properly”, leading to the lack of efficacy of the initial antidepressant, while the probability of the therapeutic response to the subsequent antidepressant remains rather high. Thus, the efficacy of an antidepressant may depend on the baseline differences in the neurochemical state contributing to the pathological “depressive” homeostasis. The heterogeneous neurochemical effects of antidepressants can determine the dissociation of existing neuronal interactions, leading to the development of the new — druginduced — homeostasis. At the same time, it is possible that stimulation of general neurotrophic processes by antidepressants may contribute to the progression and chronicity of pathology due to the ambiguous influence on certain stages of the pathological process. This determines the significance of neurophysiological studies of central disturbances in depression and search of fundamentally new neurochemical targets for the treatment of depressive states associated with various mental disorders.

A cross-sectional study on global disparities in information experiences of patients with lymphoma/CLL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18517-e18517
Author(s):  
Olufunmilayo Bamigbola ◽  
Natalie Dren ◽  
Lorna Warwick
Keyword(s):  
Side Effects ◽  
Medical Information ◽  
Information Source ◽  
Treatment Options ◽  
Information Provision ◽  
Patient Advocacy ◽  
Patient Survey ◽  
Cross Sectional ◽  
Treatment Side Effects ◽  
First Choice

e18517 Background: Patient-centricity remains a cornerstone in the care of patients with lymphoma and CLL, as informed patients are consistently associated with better outcomes and experiences. This study uses the Lymphoma Coalition (LC) 2020 Global Patient Survey (GPS) on Lymphomas and CLL to describe the global differences in the top choices for medical information among patients with lymphoma, as well as differences in their understanding of this information relating to various aspects of their care. Methods: Globally, 9,179 patients from 89 countries took part in the LC 2020 GPS. The countries were grouped into regions, and the regions with greater than 200 patients were included in the analysis (Table). The demographics of the regions were examined, and descriptive analyses of questions relating to information source preferences, information provision at diagnosis (addressing treatment options; process and stages of care; managing treatment side effects), and corresponding levels of patient understanding were performed in IBM SPSS v27. Results: Doctors were the first choice for medical information for patients in each region (SA-82%, AS- 75%, EU-69%, OC-63%, NA-61%). In EU, NA and SA, websites were the most prevalent second and third choice for information (27% and 28%; 30% and 32%; 35% and 27%, respectively). In AS, patient advocacy organisations were the most prevalent second and third choices for information (32% and 40%, respectively), while in OC, the most prevalent second and third choices were nurses (27%) and patient advocacy groups (32%) respectively. Over a fifth of NA patients were not given information on the process and stages of care and how to manage side effects of treatment (21% and 29%, respectively). About a third of patients from SA (32%) reported not getting information on treatment options. Over half of OC patients reported being given information on and completely understanding the different treatment options (51%), processes and stages of care (53%) and how to manage treatment side-effects (58%). Patients from AS were the most prevalent in reporting across the three categories, that they were given information but did not understand it (10%, 7%, 5%, respectively). Conclusions: Globally, patients with lymphoma use various avenues to source the medical information they need, and they differ in their information experiences. Access to appropriate and adequate medical information remains an essential aspect of a successful patient experience and LC advocates that this information be contextual and accessible to all patients with lymphoma. [Table: see text]

Patient Selection Criteria for Deep Brain Stimulation for Dystonia

2020 ◽  
pp. 175-184
Author(s):  
Laura S. Surillo Dahdah ◽  
Rasheda El-Nazer ◽  
Richard B. Dewey ◽  
Padraig O’Suilleabhain ◽  
Shilpa Chitnis
Keyword(s):  
Botulinum Toxin ◽  
Patient Selection ◽  
Muscle Activation ◽  
Age At Onset ◽  
Voluntary Action ◽  
Body Distribution ◽  
Segmental Dystonia ◽  
Generalized Dystonia ◽  
Patient Selection Criteria ◽  
Botulinum Toxin Injections

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. A recent revision now classifies dystonia into two axes: (1) clinical characteristics (age at onset, temporal pattern, body distribution, whether focal, segmental, or generalized; and associated features) and (2) etiology, whether idiopathic/genetic or secondary to other neurological/medical diseases. Pharmacological treatments for dystonia remain generally unsatisfactory and consist of various combinations of levodopa, anticholinergics, muscle-relaxing drugs as well as botulinum toxin injections in focal and segmental dystonia. Overall in outcomes are poor because of limited efficacy and the potential for significant side effects such as sedation and cognitive impairment. A humanitarian-device exemption from the Food and Drug Administration was issued for the treatment of medically refractory symptoms of generalized dystonia with the use of DBS. Bilateral GPi DBS surgery is effective for both generalized and focal dystonia including cervical dystonia and tardive dystonia. DBS may be the best available treatment for disabling symptoms of generalized, cervical, tardive, and other dystonia that have failed to respond to oral drugs and botulinum toxin injections (when applicable) as long as contractures have not developed, because in this situation, DBS will be ineffective. Rigorous patient selection and careful management of comorbidities are essential for favorable outcomes.

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