Treatment with l-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial

SPIRIT checklist. (PDF 60.4 kb

Metabolic markers of short and long-term exogenous DL-beta-hydroxybutyrate supplementation in episodic migraine patients: an exploratory analysis of a randomized-controlled-trial

Background: Emerging findings propose that the pathophysiology of migraine may be associated with dysfunctional metabolic mechanisms. Recent findings suggest that migraine attacks are a response to the cerebral energy deficit, and ingestion of ketone bodies stabilizes the generation of a migraine attack. Based on these findings, ketone body supplementation is postulated as a prophylactic treatment approach to restore cerebral metabolism deficiency. Metabolic markers are unexplored after exogenous ketone body supplementation in episodic migraineurs. Therefore, the present single-arm uncontrolled explorative analysis evaluated blood ketone body and glucose concentration after short and long-term 6 g exogenous DL-Mg-Ca-beta-hydroxybutyrate (DL-βHB) supplementation.Methods: The presented data are part of the MigraKet randomized-control cross-over clinical trial of 41 episodic migraineurs (Number NCT03132233). Patients were given a single dose of 6 g DL-βHB. Ketone body and glucose blood concentration were assessed before intake, 20, and 40 min after DL-βHB intake. Ketone body, glucose concentration and glycated hemoglobin values were evaluated after 12 weeks of 18 g DL-βHB ingestion (total dose), taken three times daily (6g/dose; 3x/day). Linear models explored the association between the ketone body and glucose levels.Results: Ketone body concentration increased within-group to a mean of 0.46 (0.30) mmol/L after 40 min post- DL-βHB supplementation [estimate = 0.24 mmol/L, CI = (0.20.0.27), p < 0.01]. This within-group increase of ketone body concentration did not change after repeated daily intake of DL-βHB supplementation over 12 weeks [estimate = 0.00 mmol/L, CI = (−0.03.0.04), p = 0.794]. DL-βHB intake significantly reduced blood glucose concentration within-group from a mean baseline of 4.91 (0.42) mmol/L to 4.75 (0.47) mmol/L 40 min post-DL-βHB supplementation [estimate = −0.16 mmol/L, CI = (−0.15, 0.03), p < 0.01]. Repeated DL-βHB supplementation for 12 weeks showed no change within-group in acute ketone bodies concentration [estimate = 0.00 mmol/L, CI = (−0.03.0.04), p = 0.794] and in the HbA1c value [estimate = 0.02, CI = (−0.07.0.11), p = 0.69].Conclusion: A single dose of 6 g DL-βHB significantly elevated blood ketone bodies and decreased blood glucose concentration within-group in episodic migraineurs. Long-term DL-βHB supplementation for 12 weeks showed no effect within-group on acute ketone body concentration and had not impact on HbA1c. The elevation of the ketone body concentration was moderate, indicating that nutritional ketosis was not reached. Therefore, a dose higher than 6 g of DL-βHB is required to reach the nutritional level of ketosis. ClinicalTrials.gov Identifier: NCT03132233

Patient-reported outcomes in neuromuscular disorders – health-related quality of life and psychosocial adjustment in post-polio syndrome and Duchenne muscular dystrophy

Neuromuscular disorders (NMDs) have a large impact on many aspects of life. Disabilities caused by an impaired muscle function often can lead to a wide range of secondary problems in daily life and affect psychosocial aspects such as the quality of life and psychosocial adjustment. Due to improvements in symptomatic treatments and increased life expectancy in patients with NMDs, these problems become more and more evident. In order to develop appropriate intervention programs for patients with NMDs, it is very important to evaluate patients’ quality of life and to understand its association to physical functioning thereby improving health outcomes. Furthermore, patients that are at high risk of psychosocial impairments should be detected to be able to start an early intervention. The aim of the present work is to investigate patient-reported outcomes, such as the health-related quality of life (HRQOL) and psychosocial adjustment in patients with post-polio syndrome (PPS) and Duchenne muscular dystrophy (DMD) and their association to motor abilities. First, a prospective observational study in patients with PPS is performed focusing on HRQOL, self-reported impairments and activities of daily living and their association with clinical muscle function outcomes. Afterwards, in a cross-sectional study we extensively study the HRQOL in ambulant and non-ambulant patients with DMD and its association to motor function. Finally, we focus on the psychosocial adjustment in children with DMD and its possible association to parental stress and other sociodemographic and disorder-related items

Effects of animal-assisted therapy on concentration and attention span in patients with acquired brain injury: a randomized controlled trial

OBJECTIVE: Previous studies have reported that brain-injured patients frequently suffer from cognitive impairments such as attention and concentration deficits. Numerous rehabilitation clinics offer animal-assisted therapy (AAT) to address these difficulties. The authors' aim was to investigate the immediate effects of AAT on the concentration and attention span of brain-injured patients.METHOD: Nineteen patients with acquired brain injury were included in a randomized, controlled, within-subject trial. The patients alternately received 12 standard therapy sessions (speech therapy, physiotherapy, occupational therapy) and 12 paralleled AAT sessions with comparable content. A total of 429 therapy sessions was analyzed consisting of 214 AAT and 215 control sessions. Attention span and instances of distraction were assessed via video coding in Noldus Observer. The Mehrdimensionaler Befindlichkeitsbogen ([Multidimensional Affect Rating Scale] MDBF questionnaire; Steyer, Schwenkmezger, Notz, & Eid, 1997) was used to measure the patient's self-rated alertness. Concentration was assessed through Visual Analogue Scale (VAS) via self-assessment and therapist's ratings.RESULTS: The patients' attention span did not differ whether an animal was present or not. However, patients displayed more instances of distraction during AAT. Moreover, patients rated themselves more concentrated and alert during AAT sessions. Further, therapists' evaluation of patients' concentration indicated that patients were more concentrated in AAT compared with the control condition.CONCLUSIONS: Although the patients displayed more instances of distraction while in the presence of an animal, it did not have a negative impact on their attention span. In addition, patients reported to be more alert and concentrated when an animal was present. Future studies should examine other attentional processes such as divided attention and include neurobiological correlates of attention. (PsycINFO Database Record(c) 2017 APA, all rights reserved)

Additional file 1: of Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial

Recommended items to address in a clinical trial protocol and related documents. (PDF 57 kb

Spinal cord gray matter atrophy is associated with functional decline in post-polio syndrome

OBJECTIVE To determine if patients with Post-Polio Syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline. METHODS Twenty patients diagnosed with PPS (March of Dimes Criteria) and twenty age- and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA MR-imaging at the intervertebral disc levels C2/C3-C6/C7, T9/T10 and the lumbar enlargement level (T$_{max}$ ) (0.5x0.5mm$^{2}$ in-plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self-reported fatigue, depression, pain measures were assessed. RESULTS PPS patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p=0.001), C4/C5 (p<0.001), C5/C6 (p=0.004) and T$_{max}$ (p=0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain, depression. SCGM area$_{Tmax}$ together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS-related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity. CONCLUSIONS Patients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residuals of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases. ClinicalTrials.gov (NCT03561623)