Mimicking Ding's Roll Method on Notexin-Induced Muscle Injury in Rats.

Ding's roll method is one of the most commonly used manipulations in traditional Chinese massage (Tuina) clinics and one of the most influential contemporary Tuina manipulations in China. It is based on the traditional rolling method commonly used in the one finger Zen genre and named Ding's roll method. Due to its anti-inflammatory and blood circulation-promoting effects, Ding's rolling method has sound therapeutic effects on myopathy. Because of the large area of force applied to human skin, Ding's roll method is challenging to perform on experimental animals with small skin areas, such as rats and rabbits. Additionally, the strength of Tuina applied to the human body differs from that applied to experimental animals, so it may happen that the strength is too high or too low to achieve the therapeutic effect of Tuina during the experiment. This experiment aims to create a simple massager suitable for rats based on Ding's rolling manipulation parameters (strength, frequency, Tuina duration). The device can standardize manipulation in animal experiments and reduce the variation in Tuina force applied to different animals due to subjective factors. A rat model of notexin-induced skeletal muscle injury was established, and plasma injury markers creatine kinase (CK) and fatty acid binding protein 3 (FABP3) were used to assess the therapeutic effect of Tuina on skeletal muscle injury. The results showed that this Tuina massager could reduce the levels of CK and FABP3 expression and slow down the degree of skeletal muscle injury. Therefore, the Tuina massager described here, mimicking Ding's roll method, contributes to standardizing Tuina manipulation in experimental research and is of great help for subsequent research on the molecular mechanism of Tuina for myopathy.

[Application of "eliminating stagnation and bloodletting/fire needling" in treatment of jingjin diseases].

Based on the development of conditions, the etiology and pathogenesis of jingjin (muscle region of meridian) diseases are summarized as 3 stages, i.e. stagnation due to over-exertion at early stage, manifested by tendon-muscle contracture and tenderness; cold condition due to stagnation, interaction of stasis and cold, resulting in clustered nodules at the middle stage; prolonged illness and missed/delayed treatment, leading to tendon-muscle contracture and impairment of joint function at the late stage. It is proposed that the treatment of jingjin diseases should be combined with the characteristic advantages of fire needling and bloodletting technique, on the base of "eliminating stagnation and bloodletting/fire needling". This combined therapy warming yang to resolve stasis and dispels cold to remove nodules, in which, eliminating the stagnation is conductive to the tissue regeneration, and the staging treatment is delivered in terms of the condition development at different phases.

Statin Intolerance: A Review and Update.

OBJECTIVE: To review the evidence of existing literature on the management of statin intolerance. METHODS: We searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022. RESULTS: Statin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins. CONCLUSION: Management of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.

Orthobiologic Interventions for Muscle Injuries.

Muscle injuries represent a common problem in active populations. Orthobiologics continue to be studied for their ability to improve muscle healing. To date, the basic science research for treating muscle injuries with platelet-rich plasma or stem cell remains novel. Furthermore, there are even fewer clinical studies on these topics, and their findings are inconclusive. Reviewing the literature, muscle injuries treated with ultrasound-guided leukocyte-rich PRP injections appear to have the strongest evidence. Scar formation remains a major barrier in muscle injury healing, and there is optimism for future orthobiologic treatments that target the downregulation of TGF-B, resulting in decreased scar development.

Electroacupuncture alleviates multifidus muscle injury by modulating mitochondrial function and Ca2+ uptake.

Multifidus muscles maintain the stability of the lumbar spine and play a crucial role in the pathogenesis of nonspecific lower back pain. Previous studies have shown that electroacupuncture (EA) can relieve the symptoms of low back pain and reduce injury to the lumbar multifidus muscles. In this study, a rat model of lumbar multifidus muscle injury was established by 0.05% bupivacaine injection and subsequently treated with EA at bilateral "Weizhong" (BL40) acupoints. Disruption of the function and structure of multifidus muscles, increased cytosolic Ca2+ in multifidus myocytes, and reduced mitochondrial fission and ATP production were observed in the model group. Additionally, increased expression of the mitochondrial calcium uniporter (MCU) promoted mitochondrial reuptake of Ca2+ , reversing the excessive increase in cytoplasmic Ca2+ . However, the excessive increase in MCU not only aggravated the increased cytoplasmic Ca2+ but also decreased the expression of the mitochondrial division proteins dynamin-related protein 1 (Drp1) and mitochondrial fission factor (MFF). EA inhibited the overexpression of MCU, promoted mitochondrial reuptake of Ca2+ , and reversed cytosolic Ca2+ overload. Furthermore, EA regulated the expression of the mitochondrial fission proteins Drp1 and MFF and promoted the production of ATP, helping the recovery of mitochondrial function after multifidus injury. Therefore, EA can protect against bupivacaine-induced mitochondrial dysfunction, possibly by attenuating MCU overexpression in the inner mitochondrial membrane and reducing Ca2+ overloading in muscle cells, thereby protecting mitochondrial function and maintaining the normal energy demand of muscle cells.

Electrical stimulated GLUT4 signalling attenuates critical illness-associated muscle wasting.

BACKGROUND: Critical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a by-product of critical care, attributed to impaired recovery, long-term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood; however, loss of mechanical stimuli contributes to critical illness-associated muscle atrophy and weakness. Passive mechanical loading and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care. METHODS: Rats were subjected to 8 days of critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM. RESULTS: Following 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, myosin : actin ratio, and single muscle fibre maximum force normalized to cross-sectional area (CSA; specific force) were reduced by 40-50% (P < 0.0001). ES significantly reduced the loss of soleus muscle fibre CSA and myosin : actin ratio by approximately 30% (P < 0.05) yet failed to effect specific force. RNAseq pathway analysis revealed downregulation of insulin signalling in the soleus muscle following critical care, and GLUT4 trafficking was reduced by 55% leading to an 85% reduction of muscle glycogen content (P < 0.01). ES promoted phosphofructokinase and insulin signalling pathways to control levels (P < 0.05), consistent with the maintenance of GLUT4 translocation and glycogen levels. AMPK, but not AKT, signalling pathway was stimulated following ES, where the downstream target TBC1D4 increased 3 logFC (P = 0.029) and AMPK-specific P-TBC1D4 levels were increased approximately two-fold (P = 0.06). Reduction of muscle protein degradation rather than increased synthesis promoted soleus CSA, as ES reduced E3 ubiquitin proteins, Atrogin-1 (P = 0.006) and MuRF1 (P = 0.08) by approximately 50%, downstream of AMPK-FoxO3. CONCLUSIONS: ES maintained GLUT4 translocation through increased AMPK-TBC1D4 signalling leading to improved muscle glucose homeostasis. Soleus CSA and myosin content was promoted through reduced protein degradation via AMPK-FoxO3 E3 ligases, Atrogin-1 and MuRF1. These results demonstrate chronic supramaximal ES reduces critical care associated muscle wasting, preserved glucose signalling, and reduced muscle protein degradation in CIM.

Complicated peripartum course in a patient with very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency.

Very long-chain acyl-coenzyme A (CoA) dehydrogenase (VLCAD) deficiency is an autosomal recessive fatty acid oxidation disorder characterized by rhabdomyolysis, hypoglycemia and cardiomyopathy. The general treatment approach in adult patients is based on the prevention of catabolism. High carbohydrate, low fat diet and supplementation of medium-chain triglycerides are essential in the treatment. There is little experience with pregnancy follow-up in this patient group. We present a complicated peripartum course and successful management in a patient with VLCAD deficiency. Although high-dose glucose infusion was initiated, creatine kinase levels significantly increased in the immediate postpartum period, but the patient remained asymptomatic and rhabdomyolysis resolved rapidly after increasing the glucose infusion rate.

The effect of Omega-3 polyunsaturated fatty acid supplementation on exercise-induced muscle damage.

BACKGROUND: Exercise-induced muscle damage (EIMD) results in transient muscle inflammation, strength loss, muscle soreness and may cause subsequent exercise avoidance. Omega-3 (n-3) supplementation may minimise EIMD via its anti-inflammatory properties, however, its efficacy remains unclear. METHODS: Healthy males (n = 14, 25.07 ± 4.05 years) were randomised to 3 g/day n-3 supplementation (N-3, n = 7) or placebo (PLA, n = 7). Following 4 weeks supplementation, a downhill running protocol (60 min, 65% V̇O2max, - 10% gradient) was performed. Creatine kinase (CK), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, perceived muscle soreness, maximal voluntary isometric contraction (MVIC) and peak power were quantified pre, post, and 24, 48 and 72 h post-EIMD. RESULTS: Muscle soreness was significantly lower in N-3 vs PLA group at 24 h post-EIMD (p = 0.034). IL-6 was increased in PLA (p = 0.009) but not in N-3 (p = 0.434) following EIMD, however, no significant differences were noted between groups. Peak power was significantly suppressed in PLA relative to pre-EIMD but not in N-3 group at 24 h post-EIMD. However, no significant difference in peak power output was observed between groups. MVIC, CK and TNF-α were altered by EIMD but did not differ between groups. CONCLUSION: N-3 supplementation for 4 weeks may successfully attenuate minor aspects of EIMD. Whilst not improving performance, these findings may have relevance to soreness-associated exercise avoidance.

Effects of L-Carnitine Supplementation in Patients Receiving Hemodialysis or Peritoneal Dialysis.

L-carnitine is an important factor in fatty acid metabolism, and carnitine deficiency is common in dialysis patients. This study evaluated whether L-carnitine supplementation improved muscle spasm, cardiac function, and renal anemia in dialysis patients. Eighty Japanese outpatients (62 hemodialysis (HD) patients and 18 peritoneal dialysis (PD) patients) received oral L-carnitine (600 mg/day) for 12 months; the HD patients further received intravenous L-carnitine injections (1000 mg three times/week) for 12 months, amounting to 24 months of treatment. Muscle spasm incidence was assessed using a questionnaire, and cardiac function was assessed using echocardiography. Baseline free carnitine concentrations were relatively low in patients who underwent dialysis for >4 years. Total carnitine serum concentration, free carnitine, and acylcarnitine significantly increased after oral L-carnitine treatment for 12 months, and after intravenous L-carnitine injection. There was no significant improvement in muscle spasms, although decreased muscle cramping after L-carnitine treatment was reported by 31% of patients who had undergone HD for >4 years. Hemoglobin concentrations increased significantly at 12 and 24 months in the HD group. Therefore, L-carnitine may be effective for reducing muscle cramping and improving hemoglobin levels in dialysis patients, especially those who have been undergoing dialysis for >4 years.

Effects of Hyperbaric Oxygen Therapy on Inflammation, Oxidative/Antioxidant Balance, and Muscle Damage after Acute Exercise in Normobaric, Normoxic and Hypobaric, Hypoxic Environments: A Pilot Study.

The purpose of this study was to investigate the effects of hyperbaric oxygen therapy (HBOT) on inflammation, the oxidative/antioxidant balance, and muscle damage after acute exercise in normobaric, normoxic (NN) and hypobaric, hypoxic (HH) environments. Eighteen healthy males were selected and randomly assigned to three groups: exercise in NN conditions (NN group, n = 6), HBOT treatment after exercise in NN conditions (HNN group, n = 6), and HBOT treatment after exercise in HH conditions (HHH group, n = 6). All subjects performed treadmill running for 60 min at 75-80% maximum heart rate (HRmax) exercise intensity under each condition. The HBOT treatments consisted of breathing 100% oxygen at 2.5 atmosphere absolute (ATA) for 60 min. Blood samples were collected before exercise (BE), after exercise (AE), and after HBOT (AH) to examine inflammation (fibrinogen, interleukin-6 [IL-6], and tumor necrosis factor-α (TNF-α)), the oxidative/antioxidant balance (derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP)), and muscle damage (creatine kinase (CK) and lactate dehydrogenase (LDH)). Plasma fibrinogen, serum IL-6, CK, and LDH levels were significantly increased AE compared to BE in all groups (p < 0.05). Plasma fibrinogen levels were significantly decreased AH compared to AE in all groups (p < 0.05), and the HNN group had a significantly lower AH compared to BE (p < 0.05). Serum IL-6 levels were significantly decreased AH compared to AE in the HNN and HHH groups (p < 0.05). Serum CK levels were significantly decreased AH compared to AE in the HHH group (p < 0.05). Serum LDH levels were significantly decreased AH compared to AE in the HNN and HHH groups (p < 0.05), and the NN and HNN groups had significantly higher AH serum LDH levels compared to BE (p < 0.05). These results suggest that acute exercise in both the NN and HH environments could induce temporary inflammatory responses and muscle damage, whereas HBOT treatment may be effective in alleviating exercise-induced inflammatory responses and muscle damage.

Usefulness of Carnitine Supplementation for the Complications of Liver Cirrhosis.

Carnitine is a vitamin-like substance that regulates lipid metabolism and energy production. Carnitine homeostasis is mainly regulated by dietary intake and biosynthesis in the organs, including the skeletal muscle and the liver. Therefore, liver cirrhotic patients with reduced food intake, malnutrition, biosynthetic disorder, and poor storage capacity of carnitine in the skeletal muscle and liver are more likely to experience carnitine deficiency. In particular, liver cirrhotic patients with sarcopenia are at a high risk for developing carnitine deficiency. Carnitine deficiency impairs the important metabolic processes of the liver, such as gluconeogenesis, fatty acid metabolism, albumin biosynthesis, and ammonia detoxification by the urea cycle, and causes hypoalbuminemia and hyperammonemia. Carnitine deficiency should be suspected in liver cirrhotic patients with severe malaise, hepatic encephalopathy, sarcopenia, muscle cramps, and so on. Importantly, the blood carnitine level does not always decrease in patients with liver cirrhosis, and it sometimes exceeds the normal level. Therefore, patients with liver cirrhosis should be treated as if they are in a state of relative carnitine deficiency at the liver, skeletal muscle, and mitochondrial levels, even if the blood carnitine level is not decreased. Recent clinical trials have revealed the effectiveness of carnitine supplementation for the complications of liver cirrhosis, such as hepatic encephalopathy, sarcopenia, and muscle cramps. In conclusion, carnitine deficiency is not always rare in liver cirrhosis, and it requires constant attention in the daily medical care of this disease. Carnitine supplementation might be an important strategy for improving the quality of life of patients with liver cirrhosis.

Evaluation on the effect of acupuncture on patients with sepsis-induced myopathy (ACU-SIM pilot study): A single center, propensity-score stratified, assessor-blinded, prospective pragmatic controlled trial.

BACKGROUND: Sepsis-induced myopathy (SIM) is a disease that causes motor dysfunction in patients with sepsis. There is currently no targeted treatment for this disease. Acupuncture has shown considerable efficacy in the treatment of sepsis and muscle weakness. Therefore, our research aims to explore the effects of acupuncture on the improvement of muscle structure and function in SIM patients and on activities of daily living. METHODS: The ACU-SIM pilot study is a single-center, propensity-score stratified, assessor-blinded, prospective pragmatic controlled trial (pCT) with a 1-year follow-up period. This study will be deployed in a multi-professional critical care department at a tertiary teaching hospital in Guangzhou, China. Ninety-eight intensive care unit subjects will be recruited and assigned to either the control group or the acupuncture group. Both groups will receive basic treatment for sepsis, and the acupuncture group will additionally receive acupuncture treatment. The primary outcomes will be the rectus femoris cross-sectional area, the Medical Research Council sum-score and time-to-event (defined as all-cause mortality or unplanned readmission to the intensive care unit due to invasive ventilation). The activities of daily living will be accessed by the motor item of the Functional Independence Measure. Recruitment will last for 2 years, and each patient will have a 1-year follow-up after the intervention. DISCUSSION: There is currently no research on the therapeutic effects of acupuncture on SIM. The results of this study may contribute to new knowledge regarding early muscle atrophy and the treatment effect of acupuncture in SIM patients, and the results may also direct new approaches and interventions in these patients. This trial will serve as a pilot study for an upcoming multicenter real-world study. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR-1900026308, registered on September 29th, 2019.

Proctalgia Syndromes: Update in Diagnosis and Management.

PURPOSE OF REVIEW: Functional anorectal pain syndromes are a neglected yet often disabling clinical entity resulting in significant economic and psychological burden to the patient. The aim of this review is to update the practicing gastroenterologist/coloproctologist on the diagnosis and management of these complicated disorders. RECENT FINDINGS: The updated Rome foundation diagnostic criteria (Rome IV) for functional anorectal pain subgroups chronic proctalgia (levator ani syndrome and unspecified functional anorectal pain) and acute proctalgia (proctalgia fugax) on the basis of symptom duration and digital rectal examination findings. Chronic proctalgia is thought to be secondary to paradoxical pelvic floor contraction in many patients and biofeedback to improve the defecation effort has proven effective for over 90% in the short term. Unfortunately, management of proctalgia fugax remains challenging and treatment outcomes modest at best. A number of therapies to relax the pelvic floor may be employed to improve symptoms in functional anorectal pain syndromes; however, only biofeedback to improve defaecatory dynamics in patients with levator ani syndrome has proven effectiveness in a randomized setting. Further investigation of treatment approaches in proctalgia fugax is required.

Improvement in impaired ocular accommodation by parietal acupoint therapy to relieve neck stiffness: a case report.

OBJECTIVES: Neck stiffness could lead to impaired ocular accommodation. We report two cases that visual function was improved by relieving neck stiffness. CASE PRESENTATION: (Case 1) A 34-year-old female complained of neck stiffness and visual problems after computer work. She was treated by parietal acupoint therapy (PAPT), which is a new scalp micro-acupuncture system. The evaluation of accommodative micro-fluctuations (the Fk-map) showed that increased bilateral ciliary muscle tension in the middle to near distance was relieved bilaterally, accompanied by relief of neck stiffness after treatment. (Case 2) A 43-year-old female complained of a visual problem with pressure pain on the bilateral posterior cervical muscles. Performing with PAPT improved impaired ciliary muscle tension noticeably with relief of neck stiffness after treatment. CONCLUSIONS: This is the first report on the improvement of impaired ocular accommodation with treating neck stiffness by using PAPT.

Shock wave therapy for rotator cuff disease with or without calcification.

BACKGROUND: Shock wave therapy has seen widespread use since the 1990s to treat various musculoskeletal disorders including rotator cuff disease, but evidence of its efficacy remains equivocal. OBJECTIVES: To determine the benefits and harms of shock wave therapy for rotator cuff disease, with or without calcification, and to establish its usefulness in the context of other available treatment options. SEARCH METHODS: We searched Ovid MEDLINE, Ovid Embase, CENTRAL, ClinicalTrials.gov and the WHO ICTRP up to November 2019, with no restrictions on language. We reviewed the reference lists of retrieved trials to identify potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that used quasi-randomised methods to allocate participants, investigating participants with rotator cuff disease with or without calcific deposits. We included trials of comparisons of extracorporeal or radial shock wave therapy versus any other intervention. Major outcomes were pain relief greater than 30%, mean pain score, function, patient-reported global assessment of treatment success, quality of life, number of participants experiencing adverse events and number of withdrawals due to adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and assessed the certainty of evidence using GRADE. The primary comparison was shock wave therapy compared to placebo. MAIN RESULTS: Thirty-two trials (2281 participants) met our inclusion criteria. Most trials (25) included participants with rotator cuff disease and calcific deposits, five trials included participants with rotator cuff disease and no calcific deposits, and two trials included a mixed population of participants with and without calcific deposits. Twelve trials compared shock wave therapy to placebo, 11 trials compared high-dose shock wave therapy (0.2 mJ/mm² to 0.4 mJ/mm² and above) to low-dose shock wave therapy. Single trials compared shock wave therapy to ultrasound-guided glucocorticoid needling, ultrasound-guided hyaluronic acid injection, transcutaneous electric nerve stimulation (TENS), no treatment or exercise; dual session shock wave therapy to single session therapy; and different delivery methods of shock wave therapy. Our main comparison was shock wave therapy versus placebo and results are reported for the 3 month follow up. All trials were susceptible to bias; including selection (74%), performance (62%), detection (62%), and selective reporting (45%) biases. No trial measured participant-reported pain relief of 30%. However, in one trial (74 participants), at 3 months follow up, 14/34 participants reported pain relief of 50% or greater with shock wave therapy compared with 15/40 with placebo (risk ratio (RR) 1.10, 95% confidence interval (CI) 0.62 to 1.94); low-quality evidence (downgraded for bias and imprecision). Mean pain (0 to 10 scale, higher scores indicate more pain) was 3.02 points in the placebo group and 0.78 points better (0.17 better to 1.4 better; clinically important change was 1.5 points) with shock wave therapy (9 trials, 608 participants), moderate-quality evidence (downgraded for bias). Mean function (scale 0 to 100, higher scores indicate better function) was 66 points with placebo and 7.9 points better (1.6 better to 14 better, clinically important difference 10 points) with shock wave therapy (9 trials, 612 participants), moderate-quality evidence (downgraded for bias). Participant-reported success was reported by 58/150 people in shock wave therapy group compared with 35/137 people in placebo group (RR 1.59, 95% CI 0.87 to 2.91; 6 trials, 287 participants), low-quality evidence (downgraded for bias and imprecision). None of the trials measured quality of life. Withdrawal rate or adverse event rates may not differ between extracorporeal shock wave therapy and placebo, but we are uncertain due to the small number of events. There were 11/34 withdrawals in the extracorporeal shock wave therapy group compared with 13/40 withdrawals in the placebo group (RR 0.75, 95% CI 0.43 to 1.31; 7 trials, 581 participants) low-quality evidence (downgraded for bias and imprecision); and 41/156 adverse events with extracorporeal shock wave therapy compared with 10/139 adverse events in the placebo group (RR 3.61, 95% CI 2.00 to 6.52; 5 trials, 295 participants) low-quality evidence (downgraded for bias and imprecision). Subgroup analyses indicated that there were no between-group differences in pain and function outcomes in participants who did or did not have calcific deposits in the rotator cuff. AUTHORS' CONCLUSIONS: Based upon the currently available low- to moderate-certainty evidence, there were very few clinically important benefits of shock wave therapy, and uncertainty regarding its safety. Wide clinical diversity and varying treatment protocols means that we do not know whether or not some trials tested subtherapeutic doses, possibly underestimating any potential benefits. Further trials of extracorporeal shock wave therapy for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review. A standard dose and treatment protocol should be decided upon before further research is conducted. Development of a core set of outcomes for trials of rotator cuff disease and other shoulder disorders would also facilitate our ability to synthesise the evidence.

[Follow-up study in German Hunting Terrier dogs with exercise induced metabolic myopathy]. / Verlaufsuntersuchungen bei Deutschen Jagdterriern mit belastungsabhängiger metabolischer Myopathie.

OBJECTIVE: Exercise induced metabolic myopathy in German Hunting Terrier dogs is an autosomal-recessively inherited disorder, caused by a nonsense variant of the gene encoding for the very long-chain acyl-CoA-dehydrogenase (VLCAD) enzyme. Clinical signs include exercise- induced fatigue, muscle pain and weakness. In the present study, the long-term course of this disease was investigated over a period of 1 year in 9 affected German Hunting Terriers. The dogs were treated symptomatically with oral L-carnitine, coenzyme Q10 and a special diet characterized by a low content of long-chain fatty acids and a high proportion of carbohydrates. MATERIAL AND METHODS: In 9 affected dogs, the phenotype as well as clinical, laboratory parameters, and histopathological findings are described (time point 1) and compared to follow-up examinations 1 year later (time point 2). At both time points clinical and neurological examinations, complete blood cell count, clinical chemistry profile and the concentration of brain natriuretic peptide (NT-proBNP) were investigated. RESULTS: In the follow-up examinations, the same post-exercise clinical signs were present as in the initial presentation of the homozygous dogs. Dark-brownish discoloration of the urine, weakness, myalgia as well as stiff and tetraparetic gait were apparant. All hematological values and the concentration of NT-proBNP were within the relevant reference ranges. Plasma CK and ALT activities were compared between the first presentation and the follow- up examination and no significant differences were detected (pCK = 0.31, pALT = 0.64). Signs of myopathy remained unchanged throughout the examination period. CONCLUSION AND CLINICAL RELEVANCE: Oral supplementation with L-carnitine, coenzyme Q10 and the special dietary management did not result in any improvement of clinical signs or laboratory parameters. No progression of the disease was observed. The prognosis for affected dogs remains cautious as long-term observations of affected dogs over several years are lacking. Our findings provide further important information on inherited disorders of mitochondrial ß-oxidation in dogs, especially focused on the exercise induced metabolic myopathy in the German Hunting Terrier. This may provide new insights for novel treatment modalities in conjuntion with the development of improved breeding guidelines.

Exercise therapy for muscle and lower motor neuron diseases.

Muscle and lower motor neuron diseases share a common denominator of perturbed muscle function, most often related to wasting and weakness of muscles. This leads to a number of challenges, such as restricted mobility and respiratory difficulties. Currently there is no cure for these diseases. The purpose of this review is to present research that examines the effects of exercise in muscle and lower motor neuron diseases. Evidence indicates that moderate intensity aerobic- and strength exercise is advantageous for patients with muscle diseases, without causing harmful exercise-induced muscle damage. On the contrary, motor neuron diseases show a rather blunted response from exercise training. High-intensity training is a modality that seems safe and a promising exercise method, which may circumvent neural fatigue and provide effect to patients with motor neuron disease. Although we have come far in changing the view on exercise therapy in neuromuscular diseases to a positive one, much knowledge is still needed on what dose of time, intensity and duration should be implemented for different disease and how we should provide exercise therapy to very weak, non-ambulatory and wheelchair bound patients.

Lipid storage myopathies: Current treatments and future directions.

Lipid storage myopathies (LSMs) are a heterogeneous group of genetic disorders that present with abnormal lipid storage in multiple body organs, typically muscle. Patients can clinically present with cardiomyopathy, skeletal muscle weakness, myalgia, and extreme fatigue. An early diagnosis is crucial, as some LSMs can be managed by simple nutraceutical supplementation. For example, high dosage l-carnitine is an effective intervention for patients with Primary Carnitine Deficiency (PCD). This review discusses the clinical features and management practices of PCD as well as Neutral Lipid Storage Disease (NLSD) and Multiple Acyl-CoA Dehydrogenase Deficiency (MADD). We provide a detailed summary of current clinical management strategies, highlighting issues of high-risk contraindicated treatments with case study examples not previously reviewed. Additionally, we outline current preclinical studies providing disease mechanistic insight. Lastly, we propose that a number of other conditions involving lipid metabolic dysfunction that are not classified as LSMs may share common features. These include Neurofibromatosis Type 1 (NF1) and autoimmune myopathies, including Polymyositis (PM), Dermatomyositis (DM), and Inclusion Body Myositis (IBM).

Informing the Update to the Physical Therapy Management of Congenital Muscular Torticollis Evidence-Based Clinical Practice Guideline.

PURPOSE: To systematically review the recent evidence on physical therapy (PT) diagnosis, prognosis, and intervention of congenital muscular torticollis to inform the update to the PT management of congenital muscular torticollis evidence-based clinical practice guideline. METHODS: From 2012 to 2017, 7 databases were searched for studies that informed PT diagnosis, prognosis, or intervention of infants and children with congenital muscular torticollis. Studies were appraised for risk of bias and quality. RESULTS: Twenty studies were included. No studies informed PT diagnosis. Fourteen studies informed prognosis, including factors associated with presence of a sternocleidomastoid lesion, extent of symptom resolution, treatment duration, adherence to intervention, cervical spine outcomes, and motor outcome. Six studies informed intervention including stretching frequency, microcurrent, kinesiology tape, group therapy, and postoperative PT. CONCLUSIONS: New evidence supports that low birth weight, breech presentation, and motor asymmetry are prognostic factors associated with longer treatment duration. Higher-level evidence is emerging for microcurrent intervention.

Inborn Errors of Metabolism with Myopathy: Defects of Fatty Acid Oxidation and the Carnitine Shuttle System.

Fatty acid oxidation disorders (FAODs) and carnitine shuttling defects are inborn errors of energy metabolism with associated mortality and morbidity due to cardiomyopathy, exercise intolerance, rhabdomyolysis, and liver disease with physiologic stress. Hypoglycemia is characteristically hypoketotic. Lactic acidemia and hyperammonemia may occur during decompensation. Recurrent rhabdomyolysis is debilitating. Expanded newborn screening can detect most of these disorders, allowing early, presymptomatic treatment. Treatment includes avoiding fasting and sustained extraneous exercise and providing high-calorie hydration during illness to prevent lipolysis, and medium-chain triglyceride oil supplementation in long-chain FAODs. Carnitine supplementation may be helpful. However, conventional treatment does not prevent all symptoms.