Inclusion‐body myositis presenting with facial diplegia

Introduction: The hallmark clinical presentation of inclusion‐body myositis (IBM) is slowly progressive weakness that characteristically affects the quadriceps and finger and wrist finger flexor muscles. Facial weakness can also occur, but it is typically mild and not a prominent finding. Methods: We describe the clinical features, laboratory investigations, and muscle biopsy findings in a 58‐year old man who presented with a 6‐year history of marked progressive symmetrical facial weakness. Examination also showed shoulder abduction and hip extensor weakness. Results: The patient's serum creatine kinase level was 655 U/L, and electromyography showed fibrillation potentials and myopathic motor unit potentials. A biopsy specimen of the left biceps muscle was pathognomonic for IBM. Conclusions: This patient did not have a typical presentation for IBM but rather fulfilled the pathological criteria for IBM. To our knowledge, facial diplegia has not been reported previously as a presenting manifestation of IBM. Muscle Nerve 49 : 287–289, 2014     

Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype

Introduction: The dystrophinopathies include a spectrum of muscle diseases caused by mutations in the dystrophin (DMD) gene. The clinical phenotype ranges from severe Duchenne muscular dystrophy to a mild phenotype with elevated creatine kinase (CK). Methods: Clinical and molecular assessment of 7 patients carrying a single amino acid loss in the dystrophin protein (p.His1690del) caused by a c.5068_5070delCAC tri‐nucleotide deletion in exon 36 of the DMD gene. Results: All patients were asymptomatic or oligosymptomatic and had elevated CK levels. Febrile illness, but not exercise, induced muscle symptoms in some patients. None had evidence of cardiomyopathy. Analysis of the short tandem repeat (STR)45 locus and sequencing of exon 36 of the DMD gene indicates that c.5068_5070delCAC is a founder mutation. Conclusions: The c.5068_5070delCAC locus in the DMD gene is associated with a very mild phenotype. Further study is needed to evaluate disease progression in these patients. Muscle Nerve 55 : 46–50, 2017     

Dermatomyositis presenting with rhabdomyolysis and acute renal failure; an uncommon manifestation

Rhabdomyolysis and myoglobinuria are a rare complication of dermatomyositis. Such patient can land up in acute renal failure. Recognition of this fact has important therapeutic implications as patients require immunotherapy in addition to the symptomatic treatment for renal failure. We report a case of dermatomyositis with evidence of rhabdomyolysis and myoglobinuria presenting with acute renal failure. The patient responded dramatically to corticosteroid therapy.     

GLUT1 gene mutations cause sporadic paroxysmal exercise‐induced dyskinesias

Paroxysmal exercise‐induced dyskinesias (PED) are involuntary intermittent movements triggered by prolonged physical exertion. Autosomal dominant inheritance may occur. Recently, mutations in the glucose transporter 1 (GLUT1) gene (chr. 1p35–p31.3) have been identified as a cause in some patients with autosomal dominant PED. Mutations in this gene have previously been associated with the GLUT1 deficiency syndrome. We performed mutational analysis in 10 patients with apparently sporadic PED. We identified two novel GLUT1 mutations, at least one likely to be de‐novo, in two of our patients. Onset was in early childhood. One of our patients had a predating history of childhood absence epilepsy and a current history of hemiplegic migraine as well as a family history of migraine. The other patient had no other symptoms apart from PED. Brain MRI showed cerebellar atrophy in one case. Mutations in GLUT1 are one cause of apparently sporadic PED. The detection of this has important implications for treatment as ketogenic diet has been reported to be beneficial. © 2009 Movement Disorder Society     

Ingestion of transient receptor potential channel agonists attenuates exercise‐induced muscle cramps

Introduction: Exercise‐associated muscle cramping (EAMC) is a poorly understood problem that is neuromuscular in origin. Ingestion of transient receptor potential (TRP) channel agonists has been efficacious in attenuating electrically induced muscle cramps. This study examines the effect of TRP agonist ingestion on voluntarily induced EAMC and motor function. Methods: Study 1: Thirty‐nine participants completed 2 trials after ingesting TRP agonist‐containing active treatment (A), or vehicle (V) control. Cramping in the triceps surae muscle was induced via voluntary isometric contraction. Study 2: After ingesting A or V, 31 participants performed kinematic and psychomotor tests of manual dexterity. Results: A increased precramp contraction duration (A, 36.9 ± 4.1 s; V, 27.8 ± 3.1 s), decreased cramp EMG area under the curve (A, 37.3 ± 7.7 %EMG_max·s; V, 77.2 ± 17.7 %EMG_max·s), increased contraction force to produce the cramp (A, 13.8 ± 1.8 kg; V, 9.9 ± 1.6 kg), and decreased postcramp soreness (A, 4.1 ± 0.3 arbitrary units (a.u.); V, 4.7 ± 0.3 a.u.). Kinematic and psychomotor tests were not affected. Discussion: TRP agonist ingestion attenuated EAMC characteristics without affecting motor function. Muscle Nerve 56 : 379–385, 2017     

Adjustments in the force–frequency relationship during passive and exercise‐induced hyperthermia

Introduction: We examined the extent to which fatiguing cycling exercise in the heat influences contractile function in modulating the force–frequency relationship. Methods: Before (∽37.0°C) and after (∽38.5°C) exercise (ExH) and passive (PaH) hyperthermia, an 8‐s train of stimulation at 10, 20, 50, and 100 Hz (2 s per frequency) and a potentiated twitch were evoked on the relaxed knee extensors using percutaneous stimulation. Results: ExH and PaH produced a decrease in the 20:50 Hz force ratio, indicative of low‐frequency fatigue (P < 0.01). This adjustment was more pronounced after ExH than PaH (P < 0.01). A rightward displacement in the force–frequency relationship occurred after ExH and PaH (P < 0.05) and was exacerbated by ExH (P < 0.05). Peak twitch force also decreased after ExH (P < 0.05). Conclusions: ExH reduces force summation due to development of skeletal muscle fatigue, exacerbating the shift in force–frequency to the right relative to PaH. Muscle Nerve 50 : 822–829, 2014     

Familial paroxysmal exercise‐induced dystonia: atypical presentation of autosomal dominant GTP‐cyclohydrolase 1 deficiency

Paroxysmal exercise‐induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise‐induced dystonia. The dystonia began in childhood and was only ever induced after many minutes of exercise, and was never present at rest, or on initiation of movements. In addition, family members suffered restless legs syndrome (RLS), depression, and adult‐onset Parkinsonism. The index case had low cerebrospinal fluid neurotransmitters and pterins. The PED and RLS stopped on initiation of l ‐Dopa therapy. Both live family members were found to have a nonsense mutation (p.E84X) in exon 1 of the GTP‐cyclohydrolase 1 (GCH‐1) gene. We propose that GCH‐1 mutations should be considered a genetic cause of familial PED, especially if additional clinical features of monoaminergic deficiency are present in affected individuals.     

Cardiac involvement in Dutch patients with sarcoglycanopathy: A cross‐sectional cohort and follow‐up study

Introduction: The aim of this study is to describe the frequency, nature, severity, and progression of cardiac abnormalities in a cohort of Dutch sarcoglycanopathy patients. Methods: In this cross‐sectional cohort study, patients were interviewed using a standardized questionnaire and assigned a functional score. Electrocardiography (ECG), echocardiography, and 24‐h ECG were performed. Results: Twenty‐four patients with sarcoglycanopathy had a median age of 25 years (range, 8–59 years). Beta blockers were used by 13%, and 17% used angiotensin‐converting enzyme inhibitors. ECG abnormalities were present in 5 (21%), and 4 (17%) fulfilled the criteria for dilated cardiomyopathy (DCM). There were no significant differences in median age or severity of disease between patients with or without DCM. Eleven patients were examined earlier. Median follow‐up time was 10 years. Two of the 11 patients (18%) developed DCM during follow‐up. Conclusions: Seventeen percent of the patients with sarcoglycanopathy were found to have dilated cardiomyopathy. We recommend biannual cardiac monitoring, including ECG and echocardiography. Muscle Nerve 50 : 909–913, 2014     

Deletion of TLX and social isolation impairs exercise‐induced neurogenesis in the adolescent hippocampus

Adolescence is a sensitive period of neurodevelopment during which life experiences can have profound effects on the brain. Hippocampal neurogenesis, the neurodevelopmental process of generating functional new neurons from neural stem cells, occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. The aim of this study was to investigate the influence of both TLX and isolation stress on exercise‐induced increases in neurogenesis in running and sedentary conditions during adolescence. Single‐ (isolation stress) wild type and Nr2e1^‐/‐ mice or pair‐housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during adolescence. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1^‐/‐ mice. This suggests that TLX is necessary for the pro‐neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise‐induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise‐induced increase in neurogenesis at this key point in life.     

Beneficial effects of neuropeptide galanin on reinstatement of exercise‐induced somatic and psychological trauma

Galanin is a versatile neuropeptide that is distinctly upregulated by exercise in exercise‐related tissues. Although benefits from exercise‐induced upregulation of this peptide have been identified, many issues require additional exploration. This Review summarizes the information currently available on the relationship between galanin and exercise‐induced physical and psychological damage. On the one hand, body movement, exercise damage, and exercise‐induced stress and pain significantly increase local and circulatory galanin levels. On the other hand, galanin plays an exercise‐protective role to inhibit the flexor reflex and prevent excessive movement of skeletal muscles through enhancing response threshold and reducing acetylcholine release. Additionally, elevated galanin levels can boost repair of the exercise‐induced damage in exercise‐related tissues, including peripheral nerve, skeletal muscle, blood vessel, skin, bone, articulation, and ligament. Moreover, elevated galanin levels may serve as effective signals to buffer sport‐induced stress and pain via inhibiting nociceptive signal transmission and enhancing pain threshold. This Review deepens our understanding of the profitable roles of galanin in exercise protection, exercise injury repair, and exercise‐induced stress and pain. Galanin and its agonists may be used to develop a novel preventive and therapeutic strategy to prevent and treat exercise‐induced somatic and psychological trauma. © 2016 Wiley Periodicals, Inc.