Philipp Zimmer

Exercise Intervention Studies in Patients with Peripheral Neuropathy: A Systematic Review

IntroductionPeripheral neuropathies (PNPs) encompass a large group of disorders of heterogeneous origin which can manifest themselves with sensory and/or motor deficits depending on the predominantly affected nerve fiber modality. It represents a highly prevalent disease group which can be associated with significant disability and poor recovery. Exercise has the potential to improve side effects of PNP.ObjectiveOur objective in this systematic review was to analyze exercise interventions for neuropathic patients in order to evaluate the possible benefits of exercise.MethodsThree independent reviewers used PubMed, MEDPILOT® (MEDLINE), Cochrane, and relevant reference lists to obtain the data. Relevant studies were graded according to the Oxford Levels of Evidence.ResultsEighteen studies (ten randomized controlled trials and eight controlled clinical trials) met all inclusion criteria. Three (diabetic) studies were ranked very high quality [1b (A)], nine high quality (four diabetes, one cancer, four others) [2b (B)], while six (four diabetes, two others) showed low quality (4/C). Current data suggests that exercise is a feasible, safe, and promising supportive measure for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN), suggesting that endurance training has the potential to prevent the onset of and reduce the progression of DPN. In general, balance exercises showed the highest effect on the motor as well as sensory symptoms in all types of PNP.ConclusionOverall, balance training appears to be the most effective exercise intervention. Studies focusing exclusively on strength, or a combination of endurance and strength, appear to have a lower impact. For metabolically-induced neuropathies, endurance training also plays an important role. Further research with high methodological quality needs to be conducted in order to establish evidence-based clinical recommendations for neuropathic patients.

Physical Activity in Breast Cancer Patients during Medical Treatment and in the Aftercare - a Review.

Most scientific studies regarding physical activity in cancer patients involve breast cancer patients. It is apparent that physical activity during medical treatment and aftercare is not only feasible and safe but also effective. Current studies clearly show that regular and specific endurance and/or resistance training can reduce a number of side effects caused by medical treatment. Among others, improvements in physical performance, body composition, and quality of life as well as a reduction in fatigue, have been observed. Since inactivity appears to exacerbate lymphedema, patients with lymphedema are also encouraged to exercise. Few studies have been carried out regarding physical exercise in metastatic patients. However, experts in the field also recommend regular physical activity for patients with advanced-stage breast cancer.

Effects of Exercise Interventions and Physical Activity Behavior on Cancer Related Cognitive Impairments: A Systematic Review

This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI). Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga) with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings.

Post-chemotherapy cognitive impairment in patients with B-cell non-Hodgkin lymphoma: a first comprehensive approach to determine cognitive impairments after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or rituximab and bendamustine

Abstract To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used objective and subjective measures of cognitive functions in combination with serum parameters and neuroelectric recordings. Self-perceived status of cognition, fatigue and emotional functioning were reduced in patients (n = 30) compared to healthy controls (n = 10). Cognitive performance was impaired in patients with NHL compared to controls and a norm sample (n = 1179). PCCI was more severe in patients treated with rituximab and bendamustine (BR) than in patients who received R in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients with NHL correlated with accuracy in the objective cognition test. Higher serum interleukin-6 (IL-6) concentrations were associated with higher fatigue levels. Patients with NHL and especially those who were treated with BR were affected by PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue.

Exercise-induced natural killer cell activation is driven by epigenetic modifications

Exercise has been proven to reduce the risk and progression of various diseases, such as cancer, diabetes and neurodegenerative disorders. Increasing evidence suggests that exercise affects the cytokine profile and changes distribution and function of tumor-competitive immune cells. Initial studies have shown that different exercise interventions are associated with epigenetic modifications in different tissues and cell types, such as muscle, fat, brain and blood. The present investigation examines the effect of an intense endurance run (half marathon) on global epigenetic modifications in natural killer (NK) cells in 14 cancer patients compared to 14 healthy controls. We were able to show that histone acetylation and NKG2D expression, a functional NK cell marker, were elevated for at least 24 h after the run. Thus, this is the first study to present a potential mechanism of how exercise may impact NK cell activity on the subcellular level. Further studies should focus on epigenetic mechanisms and dose-dependent effects of exercise.

Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations of tumor-competitive lymphocytes in Non-Hodgkin-Lymphoma patients-randomized controlled trial.

Physical activity is associated with decreased cancer (recurrence) risk and a reduction in treatment‐specific side effects. Exercise modulates cytokine expression and shows beneficial effects on cancer patients’ immune system. We investigated the following: (i) whether Non‐Hodgkin‐Lymphoma patients have increased serum macrophage migration inhibiting factor (MIF) and Interleukin‐6 (IL‐6) levels after immunochemotherapy; (ii) whether physical activity influences cytokine serum levels; and (iii) whether serum cytokine levels are associated with histone modifications in tumor‐competitive immune cells.

High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial:

Background: Aerobic exercise can improve cognitive performance in healthy elderly people. Objective: The aim of this study was to investigate the influence of a 3-week high-intensity aerobic exercise programme (high-intensity training group (HIT)) on cognitive performance in persons with multiple sclerosis (MS) compared with a standard exercise programme (control training (CT)). Methods: A total of 60 persons with MS (Expanded Disability Status Scale (EDSS): 1.0–6.5) were randomized to a HIT group (3×/week for 20 minutes, including five 3-minute exercise intervals at 80% of peak oxygen uptake (VO2-peak)) or a CT group (continuously 5×/week for 30 minutes/session at 65% of VO2-peak). Cognitive performance was assessed using the Brief International Cognitive Assessment for MS at entry (t0) and discharge (t1). Furthermore, VO2-peak, brain-derived neurotrophic factor, serotonin and matrix metalloproteinases (MMP)-2 and -9 were measured. Results: Compared to CT, HIT significantly improved verbal memory. Significant improvements over time in executive functions were found in both groups. Secondary outcomes indicated significant improvements in VO2-peak and a significant reduction in MMP-2 in the HIT group only. Conclusion: HIT represents a promising strategy to improve verbal memory and physical fitness in persons with MS. Further research is needed to determine the impact of exercise on biomarkers in MS.

Natural Killer Cells--An Epigenetic Perspective of Development and Regulation.

Based on their ability to recognize and eliminate various endo- and exogenous pathogens as well as pathological alterations, Natural Killer (NK) cells represent an important part of the cellular innate immune system. Although the knowledge about their function is growing, little is known about their development and regulation on the molecular level. Research of the past decade suggests that modifications of the chromatin, which do not affect the base sequence of the DNA, also known as epigenetic alterations, are strongly involved in these processes. Here, the impact of epigenetic modifications on the development as well as the expression of important activating and inhibiting NK-cell receptors and their effector function is reviewed. Furthermore, external stimuli such as physical activity and their influence on the epigenetic level are discussed.

Impact of a half marathon on cellular immune system, pro-inflammatory cytokine levels, and recovery behavior of breast cancer patients in the aftercare compared to healthy controls

Exercise has beneficial effects on cancer prevention as well as on prognosis of patients with cancer. To optimize the outcomes of exercise programs, more knowledge about the underlying mechanisms is needed. This study investigates the short‐term effects of a half marathon on immune cell proportions, pro‐inflammatory cytokine levels, and recovery behavior of patients with breast cancer in the aftercare compared to healthy controls.

Acute responses of cytokines and adipokines to aerobic exercise in relapsing vs. remitting women with multiple sclerosis

OBJECTIVE To examine the acute effect of exercise on cytokines and adipokines during relapse and the remitting phase of multiple sclerosis (MS). METHODS Thirty women with MS in the relapsing or remitting phase were matched with fifteen healthy controls. Participants performed a single-bout of aerobic exercise at 60-70% maximal heart rate. Furthermore, five women in the relapsing phase were enrolled (control relapse) and did not receive any intervention. Blood samples were taken before, immediately after, 1-h and 6-h after the exercise. RESULTS Levels of IL-10 and TNF-α in response to exercise were similar in healthy and MS remitting subjects. Compared to baseline, TNF-α levels in relapsing subjects were significantly decreased immediately after exercise. Immediately following exercise, leptin levels significantly decreased in relapsing subjects. Adiponectin and IL-6 showed no significant difference between groups. CONCLUSION After relapse, exercise does not induce inflammatory cytokine response and temporarily improves both cytokine and adipokine balance.