Whole-Body Cryostimulation in Multiple Sclerosis: A Scoping Review.

Multiple sclerosis (MS) is the most common cause of non-traumatic long-term disability in young adults. Whole-body cryostimulation (WBC) is a cold-based physical therapy known to induce physiological exercise-mimicking changes in the cardiovascular, neuromuscular, immune, and endocrine systems and to influence functional and psychological parameters by exposing the human body to cryogenic temperatures (≤-110 °C) for 2-3 min. The purpose of this scoping review is to present an overall view on the potential role of WBC as an adjuvant therapy in the treatment of MS. PubMed, ScienceDirect, Embase, and Web of Science were searched up to 30 November 2023, and a total of 13 articles were included. WBC may have beneficial antioxidant effects as a short-term adjuvant treatment in MS. There were no significant changes in antioxidant enzymes, nitric oxide levels, metalloproteinase levels, blood counts, rheology, and biochemistry. WBC can lead to a reduction in fatigue and an improvement in functional status, with a significant effect on both mental and physical well-being. There were no reported adverse effects. The results suggest that WBC may complement therapeutic options for patients with MS, as the effects of cryogenic cold stimulation have been shown to activate antioxidant processes and improve functional status, mood, anxiety, and fatigue.

Extracorporeal Shockwave Treatment as Additional Therapy in Patients with Post-Stroke Spasticity of Upper Limb-A Narrative Review.

Stroke is a severe injury of the central nervous system (CNS) and one of the leading causes of long-term disability and mortality. One of the main symptoms of neurological diseases is spasticity. This is defined as a motor condition characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks and resulting in the hyperexcitability of the stretch reflex. Rehabilitation after a stroke is focused on relearning lost skills and regaining independence. Many new methods in neurorehabilitation have been introduced. This review concentrates on the current evidence for extracorporeal shockwave therapy (ESWT) as a noninvasive alternative to treat spasticity. We present the effect of EWST and radial EWST interventions to post-stroke patients with spasticity in the upper limb. Our collected data suggest that different parameters of shockwaves can be used to achieve functional improvementsin the upper limb after a stroke. Our accumulated data imply that ESWT is safe and can be used for pain relief, reduced muscle tension, and an increased range of motion. According to many studies, complications after shockwave treatment are infrequent. Transient complications after shockwave therapy (ESWT) include redness, tingling, pain, and bruising. We reviewed clinical trials that present the possible benefits in upper-limb function after shockwave therapy for post-stroke patients. In this article, we used many database search engines, including PEDro. In the stroke rehabilitation literature, a key methodological problem is the design of double-blind studies, which very often are not feasible.

Targeting Vascular Impairment, Neuroinflammation, and Oxidative Stress Dynamics with Whole-Body Cryotherapy in Multiple Sclerosis Treatment.

Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood-brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage. The synthesis of these multifaceted aspects highlights the importance of understanding their cumulative impact on MS progression. This review reveals that the triad of vascular damage, chronic inflammation, and oxidative imbalance may be considered interdependent processes that exacerbate each other, underscoring the need for holistic and multi-targeted therapeutic approaches in MS management. There is a necessity for reevaluating MS treatment strategies to encompass these overlapping pathologies, offering insights for future research and potential therapeutic interventions. Whole-body cryotherapy (WBCT) emerges as one of the potential avenues for holistic MS management approaches which may alleviate the triad of MS progression factors in multiple ways.

Quantitative and structural changes of blood platelet cytoskeleton proteins in multiple sclerosis (MS).

Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress ß1-tubulin and ß-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding ß1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.

Impact of regular cold exposure on electrical skin resistance in patients with joint degenerative diseases.

OBJECTIVE: Common features in chronic inflammatory disease patients (CIDP) are inflammation, mental stress (MS), and autonomic nervous system imbalance. Whole-body cryotherapy (WBC) exposure and regular physical exercise are known to regulate these features. In this study, we assessed the impact of regular physical exercise and the use of WBC exposure in CIDP on the level of electrical skin resistance (SR) to evaluate the skin sympathetic nervous activity and and estimate MS levels. METHODS: SR was evaluated before and after a 10-day-period of daily physical exercise preceded or not by WBC (3 min at -110°C) in two groups of 134 CIDP (WBC vs. non-WBC groups). RESULTS: At baseline, the number of severe MS patients was similar in both groups. However, after the training period, the number of severe MS patients significantly decreased in the WBC group, only. An increase in SR (a decrease in stress level) was noted in the WBC group only, and such increase was higher in men than in women and in patients younger than 60 versus patients older than 60 years old. CONCLUSION: The use of daily WBC combined with physical exercise induced physiological adaptations and lowered the sympathetic nervous activity that may reflect a reduced level of MS in CIDP. These adaptations seem to depend on gender and age.

Objectivizing Measures of Post-Stroke Hand Rehabilitation through Multi-Disciplinary Scales.

There is a wide variety of tools and measures for rehabilitation outcomes in post-stroke patients with impairments in the upper limb and hand, such as paralysis, paresis, flaccidity, and spasticity. However, there is a lack of general recommendations for selecting the most appropriate scales, tests, and instruments to objectively evaluate therapy outcomes. Reviews on upper limb and hand measurements reveal that clinicians' choices of tools and methods are highly varied. Some clinicians and medical teams continue to employ non-standard and unverified metrics in their research and measurements. This review article aims to identify the key parameters, assessed by outcome measures and instruments, that play a crucial role in upper limb and hand rehabilitation for post-stroke patients, specifically focusing on the recovery of hand function. The review seeks to assist researchers and medical teams in selecting appropriate outcome measures when evaluating post-stroke patients. We analyze the measured factors and skills found in these outcome measures and highlight useful tools that diversify assessments and enhance result objectivity through graphical representation. The paper also describes trends and new possibilities in hand outcome measures. Clinicians frequently use proven devices, such as EMG, goniometers, and hand dynamometers. Still, there is a growing trend towards incorporating technologies, such as pose and position estimation, using artificial intelligence, or custom hand grip measurement devices. Researchers are increasingly adopting scales previously successful in orthopedic and surgical patients, recognizing their potential for objectivizing outcomes in neurological patients with post-stroke hand complications. The review included only adults over the age of 18. Outcome measures were tested for usefulness in the rehabilitation of stroke patients.

Exploring the mRNA and Plasma Protein Levels of BDNF, NT4, SIRT1, HSP27, and HSP70 in Multiple Sclerosis Patients and Healthy Controls.

Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.

Effect of SARS-CoV-2 Infection and BNT162b2 Vaccination on the mRNA Expression of Genes Associated with Angiogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The disease is multisystemic with varying degrees of severity. Unfortunately, despite intensive research, the molecular changes caused by SARS-CoV-2 remain unclear. Mechanisms affected by the virus infection include endothelial dysfunction and angiogenesis. Similarly, the vaccines developed so far affect the process of angiogenesis, contributing to the development of undesirable effects on part of the cardiovascular system. The presented research aimed to investigate the impact of the SARS-CoV-2 infection and the Pfizer Comirnaty vaccine (BNT162b2) on the molecular aspect of angiogenesis. We found that convalescents vaccinated with one dose of BNT162b2 were characterised by higher MMP-7 (metalloproteinases 7) expression than non-vaccinated convalescents and healthy volunteers vaccinated with one dose of BNT162b2. Moreover, non-vaccinated convalescents showed increased mRNA expression of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) compared to healthy volunteers vaccinated with one dose of BNT162b2. In addition, we showed significant sex differences in the expression of MMP-7. In conclusion, the results of our study suggest a significant impact of SARS-CoV-2 infection and vaccination on the course of angiogenesis at the molecular level.

Evaluating safety risks of whole-body cryotherapy/cryostimulation (WBC): a scoping review from an international consortium.

Over the two last decades, whole-body cryotherapy/cryostimulation (WBC) has emerged as an exciting non-pharmacological treatment influencing inflammatory events at a cellular and physiological level, which can result in improved sleep quality, faster neuromuscular recovery after high-intensity exercise, and chronic pain relief for patients suffering different types of diseases (fibromyalgia, rheumatism, arthritis). Some evidence even suggests that WBC has benefits on mental health (depression, anxiety disorders) and cognitive functions in both adults and older adults, due to increased circulating BDNF levels. Recently, some safety concerns have been expressed by influential public health authorities (e.g., FDA, INSERM) based on reports from patients who developed adverse events upon or following WBC treatment. However, part of the data used to support these claims involved individuals whose entire body (except head) was exposed to extreme cold vaporized liquid nitrogen while standing in a narrow bathtub. Such a procedure is known as partial-body cryotherapy (PBC), and is often erroneously mistaken to be whole-body cryotherapy. Although having similarities in terms of naming and pursued aims, these two approaches are fundamentally different. The present article reviews the available literature on the main safety concerns associated with the use of true whole-body cryotherapy. English- and French-language reports of empirical studies including case reports, case series, and randomized controlled trials (RCTs) were identified through searches of PubMed, Scopus, Cochrane, and Web of Science electronic databases. Five case reports and two RCTs were included for a total of 16 documented adverse events (AEs). A critical in-depth evaluation of these AEs (type, severity, context of onset, participant's medical background, follow-up) is proposed and used to illustrate that WBC-related safety risks are within acceptable limits and can be proactively prevented by adhering to existing recommendations, contraindications, and commonsense guidelines.

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation-A Prospective Observational Study.

The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

Immersion Therapy with Head-Mounted Display for Rehabilitation of the Upper Limb after Stroke-Review.

Immersive virtual therapy technology is a new method that uses head-mounted displays for rehabilitation purposes. It offers a realistic experience that puts the user in a virtual reality. This new type of therapy is used in the rehabilitation of stroke patients. Many patients after this disease have complications related to the upper extremities that limit independence in their everyday life, which affects the functioning of society. Conventional neurological rehabilitation can be supplemented by the use of immersive virtual therapy. The system allows patients with upper limb dysfunction to perform a motor and task-oriented training in virtual reality that is individually tailored to their performance. The complete immersion therapy itself is researched and evaluated by medical teams to determine the suitability for rehabilitation of the upper limb after a stroke. The purpose of this article is to provide an overview of the latest research (2019-2022) on immersive virtual reality with head-mounted displays using in rehabilitation of the upper extremities of stroke patients.

The Role of Vitamin D in Stroke Prevention and the Effects of Its Supplementation for Post-Stroke Rehabilitation: A Narrative Review.

Hypovitaminosis D is a serious public health problem, representing an independent factor in mortality among the general population. Vitamin D deficiency may affect up to one billion people worldwide. Recently, the potential association between vitamin D levels and stroke has gained increasing attention. Many studies suggest that maintaining normal serum vitamin D levels is associated with improvement of the cardiovascular system and a reduction in stroke risk. As a neurosteroid, vitamin D influences brain development and function and immunomodulation and affects brain neuroplasticity. It supports many processes that maintain homeostasis in the body. As stroke is the second most common cause of death worldwide, more studies are needed to confirm the positive effects of vitamin D supplementation, its dosage at different stages of the disease, method of determination, and effect on stroke onset and recovery. Many studies on stroke survivors indicate that serum vitamin D levels only offer insignificant benefits and are not beneficial to recovery. This review article aims to highlight recent publications that have examined the potential of vitamin D supplementation to improve rehabilitation outcomes in stroke survivors. Particular attention has been paid to stroke prevention.

Variation of genes encoding nitric oxide synthases and antioxidant enzymes as potential risks of multiple sclerosis development: a preliminary study.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by a variable clinical course and diverse pathophysiology, including nitrative and oxidative stresses as well as inflammation. We aimed to detect the potential association between five selected single-nucleotide polymorphisms (SNPs) in genes encoding nitric oxide synthetases as well as antioxidant enzymes and the development of MS in a Polish population. Genomic DNA was isolated from peripheral blood collected from 142 MS patients and 140 controls. Using Taq-Man® probes, we genotyped the following SNPs: rs1879417 in NOS1, and rs2297518 in NOS2 as well as rs4880 in SOD2, rs7943316 in CAT, rs713041 in GPX4. In the case of rs2297518, the C/C genotype and C allele SNP were associated with an enhanced occurrence of MS, while the C/T, T/T genotypes, and T allele of the same polymorphism reduced this risk. Moreover, the C/C homozygote and C allele of the rs4880 SNP reduced MS risk, while the T allele increased the risk. In addition, the A/T heterozygote of rs7943316 polymorphism was associated with an increased risk of MS occurrence. We also detected that the C/C genotype and C allele of rs713041 decreased the risk of MS, whereas the T/T genotype and T allele increased this risk. In conclusion, the results of our study suggest some links between polymorphic variability in the nitrative/oxidative stress-related genes and the risk of MS development in the Polish population.

Neuroimaging Techniques as Potential Tools for Assessment of Angiogenesis and Neuroplasticity Processes after Stroke and Their Clinical Implications for Rehabilitation and Stroke Recovery Prognosis.

Stroke as the most frequent cause of disability is a challenge for the healthcare system as well as an important socio-economic issue. Therefore, there are currently a lot of studies dedicated to stroke recovery. Stroke recovery processes include angiogenesis and neuroplasticity and advances in neuroimaging techniques may provide indirect description of this action and become quantifiable indicators of these processes as well as responses to the therapeutical interventions. This means that neuroimaging and neurophysiological methods can be used as biomarkers-to make a prognosis of the course of stroke recovery and define patients with great potential of improvement after treatment. This approach is most likely to lead to novel rehabilitation strategies based on categorizing individuals for personalized treatment. In this review article, we introduce neuroimaging techniques dedicated to stroke recovery analysis with reference to angiogenesis and neuroplasticity processes. The most beneficial for personalized rehabilitation are multimodal panels of stroke recovery biomarkers, including neuroimaging and neurophysiological, genetic-molecular and clinical scales.

Benefits from Repetitive Transcranial Magnetic Stimulation in Post-Stroke Rehabilitation.

Stroke is an acute neurovascular central nervous system (CNS) injury and one of the main causes of long-term disability and mortality. Post-stroke rehabilitation as part of recovery is focused on relearning lost skills and regaining independence as much as possible. Many novel strategies in neurorehabilitation have been introduced. This review focuses on current evidence of the effectiveness of repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation (NIBS), in post-stroke rehabilitation. Moreover, we present the effects of specific interventions, such as low-frequency or high-frequency rTMS therapy, on motor function, cognitive function, depression, and aphasia in post-stroke patients. Collected data suggest that high-frequency stimulation (5 Hz and beyond) produces an increase in cortical excitability, whereas low-frequency stimulation (≤1 Hz) decreases cortical excitability. Accumulated data suggest that rTMS is safe and can be used to modulate cortical excitability, which may improve overall performance. Side effects such as tingling sensation on the skin of the skull or headache are possible. Serious side effects such as epileptic seizures can be avoided by adhering to international safety guidelines. We reviewed clinical studies that present promising results in general recovery and stimulating neuroplasticity. This article is an overview of the current rTMS state of knowledge related to benefits in stroke, as well as its cellular and molecular mechanisms. In the stroke rehabilitation literature, there is a key methodological problem of creating double-blinding studies, which are very often impossible to conduct.

Cryostimulation for Post-exercise Recovery in Athletes: A Consensus and Position Paper.

Recovery after exercise is a crucial key in preventing muscle injuries and in speeding up the processes to return to homeostasis level. There are several ways of developing a recovery strategy with the use of different kinds of traditional and up-to-date techniques. The use of cold has traditionally been used after physical exercise for recovery purposes. In recent years, the use of whole-body cryotherapy/cryostimulation (WBC; an extreme cold stimulation lasting 1-4 min and given in a cold room at a temperature comprised from -60 to -195°C) has been tremendously increased for such purposes. However, there are controversies about the benefits that the use of this technique may provide. Therefore, the main objectives of this paper are to describe what is whole body cryotherapy/cryostimulation, review and debate the benefits that its use may provide, present practical considerations and applications, and emphasize the need of customization depending on the context, the purpose, and the subject's characteristics. This review is written by international experts from the working group on WBC from the International Institute of Refrigeration.

Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing-Remitting from Secondary Progressive Multiple Sclerosis. A Review.

Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing-remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.

Unusual Bioactive Compounds with Antioxidant Properties in Adjuvant Therapy Supporting Cognition Impairment in Age-Related Neurodegenerative Disorders.

Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges.