Preventive Effect of Neuromuscular Training on Chemotherapy-Induced Neuropathy: A Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival. Objective: To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN. Design, Setting, and Participants: This prospective multicenter randomized clinical trial (STOP) followed up patients over 5 years at 4 centers in or near Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants were recruited from May 2014 to November 2020. Data were last analyzed in June 2021. Interventions: Participants in the intervention groups performed supervised SMT or WBV training sessions twice a week, each lasting approximately 15 to 30 minutes, concomitant to medical therapy. Main Outcomes and Measures: The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis. Results: A total of 1605 patients were screened, and 1196 patients did not meet all inclusion criteria, with 251 further excluded or declining participation. A total of 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat-MH). Patients receiving vinca alkaloids and performing SMT benefited the most. Results were more pronounced in a per-protocol analysis (>75% participation in the intervention) (SMT, 8 of 28 [28.6%; 95% CI, 16.6%-40.5%] and WBV, 9 of 24 [37.5%; 95% CI, 24.4%-50.5%] vs TAU, 22 of 30 [73.3%; 95% CI, 61.6%-85.6%]). Improvements in favor of SMT compared to TAU were found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality. Conclusion and Relevance: This randomized clinical trial provides initial evidence that neuromuscular training decreases the onset of CIPN. Trial Registration: German Clinical Trials Register: DRKS00006088.

Therapeutic Potential of Electromyostimulation (EMS) in Critically Ill Patients-A Systematic Review.

Ample evidence exists that intensive care unit (ICU) treatment and invasive ventilation induce a transient or permanent decline in muscle mass and function. The functional deficit is often called ICU-acquired weakness with critical illness polyneuropathy (CIP) and/or myopathy (CIM) being the major underlying causes. Histopathological studies in ICU patients indicate loss of myosin filaments, muscle fiber necrosis, atrophy of both muscle fiber types as well as axonal degeneration. Besides medical prevention of risk factors such as sepsis, hyperglycemia and pneumonia, treatment is limited to early passive and active mobilization and one third of CIP/CIM patients discharged from ICU never regain their pre-hospitalization constitution. Electromyostimulation [EMS, also termed neuromuscular electrical stimulation (NMES)] is known to improve strength and function of healthy and already atrophied muscle, and may increase muscle blood flow and induce angiogenesis as well as beneficial systemic vascular adaptations. This systematic review aimed to investigate evidence from randomized controlled trails (RCTs) on the efficacy of EMS to improve the condition of critically ill patients treated on ICU. A systematic search of the literature was conducted using PubMed (Medline), CENTRAL (including Embase and CINAHL), and Google Scholar. Out of 1,917 identified records, 26 articles (1,312 patients) fulfilled the eligibility criteria of investigating at least one functional measure including muscle function, functional independence, or weaning outcomes using a RCT design in critically ill ICU patients. A qualitative approach was used, and results were structured by 1) stimulated muscles/muscle area (quadriceps muscle only; two to four leg muscle groups; legs and arms; chest and abdomen) and 2) treatment duration (≤10 days, >10 days). Stimulation parameters (impulse frequency, pulse width, intensity, duty cycle) were also collected and the net EMS treatment time was calculated. A high grade of heterogeneity between studies was detected with major cofactors being the analyzed patient group and selected outcome variable. The overall efficacy of EMS was inconclusive and neither treatment duration, stimulation site or net EMS treatment time had clear effects on study outcomes. Based on our findings, we provide practical recommendations and suggestions for future studies investigating the therapeutic efficacy of EMS in critically ill patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021262287].

Exercise and Neuropathy: Systematic Review with Meta-Analysis.

INTRODUCTION: Peripheral neuropathies are a prevalent, heterogeneous group of diseases of the peripheral nervous system. Symptoms are often debilitating, difficult to treat, and usually become chronic. Not only do they diminish patients' quality of life, but they can also affect medical therapy and lead to complications. To date, for most conditions there are no evidence-based causal treatment options available. Research has increased considerably since the last review in 2014 regarding the therapeutic potential of exercise interventions for patients with polyneuropathy. OBJECTIVE: Our objective in this systematic review with meta-analysis was to analyze exercise interventions for neuropathic patients in order to update a systematic review from 2014 and to evaluate the potential benefits of exercise on neuropathies of different origin that can then be translated into practice. METHODS: Two independent reviewers performed a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria according to the PICOS approach were: neuropathic patients, exercise interventions only, an inactive or non-exercising control group, and solely randomized controlled trials with the following outcome parameters: neuropathic symptoms, balance parameters, functional mobility, gait, health-related quality of life, and HbA1c (glycated hemoglobin). RESULTS: A total of 41 randomized, controlled trials met all inclusion criteria, 20 of which could be included in the quantitative analysis. Study quality varied from moderate to high. Current data further support the hypothesis that exercise is beneficial for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN) (27 studies) as well as for chemotherapy-induced peripheral neuropathy (CIPN) (nine studies), while there are only few studies (five) on all other causes of neuropathy. We found standardized mean differences in favor of the exercise group of 0.27-2.00 for static balance, Berg Balance Scale, Timed-up-and-go-test, nerve conduction velocity of peroneal and sural nerve as well as for HbA1c in patients with DPN, and standardized mean differences of 0.43-0.75 for static balance, quality of life, and neuropathy-induced symptoms in patients with CIPN. CONCLUSION: For DPN, evidence-based recommendations can now be made, suggesting a combination of endurance and sensorimotor training to be most beneficial. For patients with CIPN, sensorimotor training remains the most crucial component. For all other neuropathies, more high-quality research is needed to derive evidence-based recommendations. Overall, it seems that sensorimotor training has great potential to target most neuropathies and combined with endurance training is therefore currently the best treatment option for neuropathies. REGISTRATION NUMBER: (PROSPERO 2019 CRD42019124583)/16.04.2019.

Injuries and Use of Safety Equipment in Stand-up Paddle Boarding.

BACKGROUND: Stand-up paddleboarding (SUP) is a water sport that has gained in popularity. Still, very little is known about its injury profile. PURPOSE: To analyze the incidence, mechanisms, and risk factors for SUP-related injuries in mainly calm waters and the use of safety equipment. STUDY DESIGN: Descriptive epidemiology study. METHODS: The authors distributed an online survey that gathered information on characteristics, injury history over the past 12 months, use of (safety) equipment, and health issues of SUP riders in German-speaking countries. RESULTS: A total of 438 participants completed the survey. The mean participant age was 45 years (range, 8-82 years), 48% were female athletes, and 19.6% took part in competitions. Over the past 12 months, 72 (17%) of 431 respondents experienced a SUP-related injury, resulting in an overall incidence rate (IR) of 1.95 injuries per 1000 hours of activity. Male competitive athletes using a hardboard had the highest risk of injury. The IR for competitive riders was higher (3.21 injuries per 1000 hours) than that for recreational riders (1.41 injuries per 1000 hours). Mechanisms of injury were overuse (n = 29) and contact with the board (n = 18) or ground (n = 12). Injuries affected mainly muscles/tendons and joints of the upper arm/shoulder (n = 20), followed by wrist/hand (n = 18), knee (n = 16), elbow/forearm (n = 12), and foot (n = 11). The highest risk of injury occurred when paddling in wild water (33.3%), followed by SUP surfing (29.4%), and the lowest risk occurred while paddling on a lake (16.1%). A life vest was always used by 27, depending on the situation by 201, and never by 202 participants; a leash was always used by 161, depending on the situation by 244, and never by 26 participants. Of the 272 participants who paddled in winter, 253 wore a drysuit or wetsuit, whereas 19 paddled without any special clothing. CONCLUSION: SUP-related injuries predominantly happened in wild water or while SUP surfing, and male competitive athletes using a hardboard had the highest risk of injury. The main mechanisms of injury were overuse and hitting the board or ground. The upper extremity was more prone to injury, followed by the knee and foot. More effort should be made to educate paddlers on the necessity and correct use of the life vest, leash, and specialized outfits.

Individually tailored whole-body vibration training to reduce symptoms of chemotherapy-induced peripheral neuropathy: study protocol of a randomised controlled trial-VANISH.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically meaningful side effect of cancer treatment. CIPN is induced by neurotoxic agents, causing severe sensory and/or motor deficits, resulting in disability and poor recovery, reducing patients' quality of life and limiting medical therapy. To date, effective treatment options are lacking. Whole-body vibration (WBV) training can attenuate motor and sensory deficits. We are conducting a two-armed, multicentre, assessor-blinded, randomised controlled trial, to investigate the effects of WBV on relevant symptoms of CIPN and determine the training characteristics. METHODS AND ANALYSIS: In this ongoing study, 44 patients who have completed therapy in the past 3 months, with a neurologically confirmed CIPN are assessed before and after a 12-week intervention and follow-up. The intervention group receives WBV twice a week. Exercises are individually tailored according to the initially determined optimal neuromuscular response. The control group receives care as usual.Primary endpoint is the patient reported reduction of CIPN-related symptoms (Functional Assessment of Cancer Therapy/Gynaecology Oncology Group-Neurotoxicity). Secondary endpoints are compound muscle action potentials, distal motor latency, conduction velocity, F-waves from the tibial and peroneal nerve, antidromic sensory nerve conduction studies of the sural nerve, normalised electromyographic activity, peripheral deep sensitivity, proprioception, balance, pain, the feasibility of training settings, quality of life and the level of physical activity. AIM, ETHICS AND DISSEMINATION: The study was approved by both responsible ethics committees. (1) Our results may contribute to a better understanding of the effects of WBV on motor and sensory functions and (2) may provide information whether WBV at the most effective setting, is feasible for neuropathic patients. (3) Our results may also contribute to improve supportive care in oncology, thereby enhancing quality of life and enabling the optimal medical therapy. All results will be published in international peer-reviewed journals as well as a manual for clinical practice. TRIAL REGISTRATION NUMBER: NCT03032718.

The preventive effect of sensorimotor- and vibration exercises on the onset of Oxaliplatin- or vinca-alkaloid induced peripheral neuropathies - STOP.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait. These symptoms not only affect activities of daily living, subsequently reducing patients' quality of life, they have far more become a decisive limiting factor for medical therapy, causing treatment delays, dose reductions, or even discontinuation of therapy, which can affect the outcome and compromise survival. To date, CIPN cannot be prevented and its occurrence presents a diagnostic dilemma since approved and effective treatment options are lacking. Promising results have recently been achieved with exercise. We have revealed that sensorimotor training (SMT) or whole body vibration (WBV) can reduce the symptoms of CIPN and attenuate motor and sensory deficits. We furthermore detected a tendency that it may also have a preventive effect on the onset of CIPN. METHODS: We are therefore conducting a prospective, multicentre, controlled clinical trial involving 236 oncological patients receiving either oxaliplatin (N = 118) or vinca-alkaloid (N = 118) who are randomized to one of two interventions (SMT or WBV) or a treatment as usual (TAU) group. Primary endpoint is the time to incidence of neurologically confirmed CIPN. Secondary endpoints are pain, maintenance of the functionality of sensory as well as motor nerve fibres as well as the level of physical activity. The baseline assessment is performed prior to the first cycle of chemotherapy. Subsequent follow-up assessments are conducted at 12 weeks, after completion of chemotherapy, and at a 3-month follow-up. Patients who develop CIPN receive an additional assessment at this time point, as it represents the primary endpoint. DISCUSSION: We hypothesize that SMT and WBV prevent the onset or delay the progression of CIPN, decrease the likelihood of dose reductions or discontinuation of cancer treatment and improve patients' quality of life. TRIAL REGISTRATION: Deutsche Register Klinischer Studien ( DRKS00006088 , registered 07.05.2014).

[30-year-old Patient with suspected Marfan Syndrome and Progressive Gait disturbance]. / 30-jähriger Patient mit V. a. Marfan-Syndrom und zunehmend beeinträchtigter Gehfähigkeit.

History A 30-year-old man presented with a history of progressive muscle weakness, difficulty in concentrating, and a slender habitus since early childhood. Marfan syndrome was suspected since the age of 14. Examinations 13 years later he was examined by Marfan experts and by genetic testing and Marfan syndrome could not be confirmed. Further neurological examination revealed the suspected diagnosis of myotonic dystrophy type 1, which was confirmed by genetic testing. Treatment and course Similar to Marfan syndrome, myotonic dystrophy is a multisystemic disorder with the risk of cardiac arrythmias. It is necessary to provide an interdisciplinary care by neurologists, internists, ophthalmologists, speech therapists, and physiotherapists. Conclusion It is not enough to take the habitus as the principle sign to diagnose Marfan syndrome. Furthermore, it is essential to consider symptoms that are not typical for Marfan syndrome, such as cognitive deficiencies or progressive paresis.

The laser-pointer assisted angle reproduction test for evaluation of proprioceptive shoulder function in patients with instability.

INTRODUCTION: Over the last decade, proprioceptive function gained increasing attention in joint disorders such as instability of the shoulder. Common tests for evaluation of proprioception are limited by their complexity and high technical demands. Thus, they are hardly applicable during daily routine. Our hypothesis was that the simplified "laser-pointer assisted angle reproduction test" (LP-ART) presented here allows for clinically feasible assessment of proprioceptive shoulder function. METHODS: Active angle reproduction capability as an aspect of sensorimotor function was evaluated with the new method in patients with shoulder instability (n = 24) and healthy controls (n = 24). 15 patients had traumatic, 9 non-traumatic anterior instability (6 bilateral), 17 were treated surgically, 13 non-operatively. Tests were performed in flexion and abduction in different angles (55°, 90°, 125°) in randomized order. RESULTS: Angle reproduction capability was worst below shoulder level (55°) in all groups. Best results were achieved at shoulder level (90°). Healthy controls showed overall better results than patients with instability. Patients after surgical stabilization had better results in 55° and 90° abduction compared to instability patients before surgery. CONCLUSIONS: The new LP-ART presented here is a technically simple, yet effective instrument for evaluation of the proprioceptive function of the shoulder. In contrast to former test setups it is feasible in daily routine. Compared to healthy controls, patients with unstable shoulder joints show significant proprioceptive disorders that can be quantified by the LP-ART.

Orienting of attention in unmedicated patients with schizophrenia, prodromal subjects and healthy relatives.

In typical orienting of attention tasks subjects have to respond as fast as possible to targets which appear in the periphery of the visual field and are preceded by spatial cues (e.g. brightening of a peripheral box where the target may subsequently appear). Reaction times (RT) are facilitated when cue and target appear at the same location (valid cueing) and the cue target interval is short (<250 ms). However, RTs slow down again when the target follows a valid cue after an interval of 250 ms and longer. This latter phenomenon is called Inhibition of Return (IOR) and is thought to reflect an automatic, inhibitory mechanism to protect the organism from redundant and distracting stimuli. Deficits of IOR were repeatedly reported in patients with schizophrenia. However, the role of medications and the nature of the deficit (trait or vulnerability indicator?) were unclear. In the present study we examined 15 unmedicated patients with schizophrenia (age: 31.2+/-11.1, m/f: 11/4, global scores SAPS: 48.33+/-33.09, SANS: 19.22+/-26.16), 29 subjects who were putatively in a prodromal state of psychosis, 30 first-degree relatives, another 8 first-degree relatives who had one child and at least one more relative with schizophrenia, and 50 healthy controls. We found an impairment of IOR only in the unmedicated patient group. In conclusion, blunted IOR in schizophrenia is not secondary to medications. According to this and previous studies blunted IOR may be most probably viewed as a trait cognitive feature of the schizophrenic disorder.