Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2)

A previous study in proximal myotonic myopathy (PROMM/DM-2) and myotonic dystrophy type 1 (DM-1) using brain positron emission tomography demonstrated a reduced cerebral blood flow in the frontal and temporal regions associated with cognitive impairment. The objective was to investigate further cognitive and behavioural aspects in a new series of patients with DM-1 and PROMM/DM-2. Nineteen patients with genetically determined PROMM/DM-2 and 21 patients with moderately severe DM-1 underwent neuropsychological testing and neuropsychiatric interviews. DM-1 and PROMM/DM-2 patients had significantly lower scores on tests of frontal lobe function compared to controls. Neuropsychiatric interviews demonstrated an avoidant trait personality disorder in both patient groups. Brain single photon emission computed tomography showed frontal and parieto-occipital hypoperfusion. The results suggest that there is a specific cognitive and behavioural profile in PROMM/DM-2 and in DM-1, and that this profile is associated with hypoperfusion in frontal and parieto-occipital regions of the brain.     

Shank sign in myotonic dystrophy type-1 (DM-1).

This study aimed to examine the specific shape of the shoulders and arms as a result of selective changes in muscle bulk, which could be diagnostic of myotonic dystrophy type-1 (DM-1). Thirty-two DM-1 patients from 18 families were asked to abduct their arms to about 90 degrees with elbows flexed to 90 degrees in such a manner that the hands were directed upwards. Examination from behind revealed a normal appearance of the shoulder girdle and proximal upper arm musculature, and sudden tapering thereafter, due to wasting of biceps, triceps and forearm muscles. The upper limbs looked like the shanks of an animal. 'Shank sign' was visible in 25 (78%) patients with DM-1 but not in any with DM-2 or other common muscular dystrophies such as Becker's dystrophy, limb-girdle syndrome or facioscapulohumeral dystrophy. Patients with positive signs included nine with very mild myotonia, suggesting its clinical utility in difficult cases.     

Cognitive deficits and CTG repeat expansion size in classical myotonic dystrophy type 1 (DM1)

Background  

This study was designed to investigate cognitive abilities and their correlations with CTG repeat expansion size in classical Myotonic dystrophy type 1 (DM1), given that earlier studies have indicated cognitive deficits, possibly correlating with blood CTG repeats expansion size.     

Metabolic syndrome in patients with myotonic dystrophy type 1

Introduction: The aim of this study was to assess the frequency and features of metabolic syndrome (MetS) in myotonic dystrophy type 1 (DM1). Methods: We studied 66 DM1 patients (50% men, aged 41.9 ± 10.5 years, disease duration of 19.3 ± 8.6 years). New worldwide consensus criteria for MetS from 2009 were used. Results: Components of MetS were present at the following frequencies: hypertriglyceridemia 67%; low HDL cholesterol 35%; hypertension 18%; central obesity 14%; and hyperglycemia 9%. MetS was present in 11 (17%) patients. The presence of MetS was not associated with patients' gender, age, disease severity, disease duration, or CTG repeat length (P > 0.05). Patients with MetS had significantly lower total SF‐36 scores as a measure of quality of life in comparison to patients without MetS (P < 0.05). Conclusion: Although certain components of MetS were very frequent in patients with DM1, only 17% met the criteria for MetS. Muscle Nerve 52 : 273–277, 2015     

Aerobic training in patients with myotonic dystrophy type 1

The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter increased significantly, and creatine kinase did not increase with training. The study indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy.     

Winged scapula in patients with myotonic dystrophy type 1

We report two patients with myotonic dystrophy type 1 (DM1) showing winged scapula in a single family. Genomic analysis revealed a marked expansion of CTG repeats in the 3' untranslated region; 1100 in patient 1 and 667 in patient 2. Muscle MRI revealed marked atrophy in the serratus anterior muscle in both patients. Muscle biopsy findings showed central nuclei and variations in fiber size. One of the patients showed ragged red fibers in muscles of the biceps brachii. To our knowledge, this is the first report of typical winged scapula in DM1.     

Transcranial sonography in patients with myotonic dystrophy type 1

Introduction: In this study we analyzed transcranial sonography (TCS) in patients with myotonic dystrophy type 1 (DM1). Methods: This cross‐sectional study included 66 DM1 patients and 55 matched healthy controls (HCs). Echogenicity of the brainstem raphe (BR) and substantia nigra (SN) and third ventricle width (DTV) were assessed by TCS. Results: BR hypoechogenicity was more common in DM1 patients than in HCs (37.7% vs. 7.8%, P < 0.01). Patients with depression or fatigue were more likely to have BR hypoechogenicity (80.0% vs. 29.4%, P < 0.01 and 51.9% vs. 24.2%, P < 0.05, respectively). Both hypoechogenicity and hyperechogenicity of SN were more frequent in DM1 patients than in controls (26.2% vs. 10.9% and 13.1% vs. 1.8%, respectively, P < 0.01). DTV was increased in DM1 patients compared with HCs (6.0 ± 1.4 vs. 4.9 ± 0.9 mm, P < 0.01). Conclusion: TCS can offer new insight into structural changes of several cerebral areas in patients with DM1. Muscle Nerve 50:278–282, 2014     

Muscle phenotype in patients with myotonic dystrophy type 1

Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand‐held dynamometry. Myotonia was evaluated by a handgrip test and by analyzing the decrement of the compound muscle action potential. Muscle biopsies were assessed for morphological changes and Na⁺‐K⁺ pump content. Results: Muscle strength correlated with a decline in Na⁺‐K⁺ pump content (r = 0.60, P < 0.001) and with CTG expansion. CTG expansion did not correlate with severity of myotonia, proximal histopathological changes, or Na⁺‐K⁺ pump content. Histopathologically, we found few centrally placed nuclei (range 0.2–6.9%). Conclusions: The main findings of this study are that muscle weakness correlated inversely with CTG expansion and that central nuclei are not a prominent feature of proximal muscles in DM1. Muscle Nerve 47:409‐415, 2013     

Cognitive impairment in myotonic dystrophy type 1 (DM1)

OBJECTIVE: To characterize the progression of the cognitive involvement in patients affected by myotonic dystrophy type 1 (DM1) by a longitudinal neuropsychological follow-up study. METHODS: In a previous study we documented an ageing-related decline of frontal and temporal cognitive functions in juvenile/adult forms of DM1, irrespectively of the n(CTG) in leukocytes and the severity of muscle weakness. Here we present the results of a neuropsychological follow-up study performed in 34 out of 70 DM1 patients previously studied. Patients were divided into four groups according to their genotype (E1:50-150; E2:150-500; E3:500-1000; E4: >1000 CTG). The neuropsychological test battery included MMSE, memory, linguistic, level, praxis, attentional and frontal-executive tasks. Statistical analysis was performed by One way MANOVA with repeated measures analysis and by Wilcoxon match paired test. RESULTS: The whole group of patients showed a significant deterioration in linguistic functions, together with a tendency towards decline in executive abilities, confirming a predominant involvement of cognitive functions subserved by fronto-temporal areas. We found no significant correlation between the progression of cognitive decline and the n(CTG) in leukocytes. Moreover, we observed that patients belonging to E2 group, with the highest mean age, got scores lower than E3 patients, with particular regard both to linguistic and executive tasks. CONCLUSIONS: These data support our previous hypothesis that the cognitive damage is confined to frontotemporal functions in adult DM1 patients, with a tendency towards a decline with aging.     

Endocrine function in 97 patients with myotonic dystrophy type 1

The aim of this study was to investigate the endocrine function and its association to number of CTG repeats in patients with myotonic dystrophy type 1 (DM1). Concentration of various hormones and metabolites in venous blood was used to assess the endocrine function in 97 patients with DM1. Correlation with CTG(n) expansion size was investigated with the Pearson correlation test. Eighteen percent of the DM1 patients had hyperparathyroidism with increased PTH compared with 0.5% in the background population. Of these, 16% had normocalcemia and 2% had hypercalcemia. An additional 3% had hypercalcemia without elevation of PTH; 7% had abnormal TSH values (2% subnormal and 5% elevated TSH levels); 5% of the patients had type 2 diabetes mellitus; 17% of the male DM1 patients had increased LH and low levels of plasma testosterone indicating absolute androgen insufficiency. Another 21% had increased LH, but normal testosterone levels, indicating relative insufficiency. Numbers of CTG repeats correlated directly with plasma PTH, phosphate, LH, and tended to correlate with plasma testosterone for males. This is the largest study of endocrine dysfunction in a cohort of Caucasian patients with DM1. We found that patients with DM1 have an increased risk of abnormal endocrine function, particularly calcium metabolism disorders. However, the endocrine dysfunction appears not to be of clinical significance in all of the cases. Finally, we found correlations between CTG(n) expansion size and plasma PTH, phosphate, and testosterone, and neck flexion strength.     

强直性肌营养不良1型患者临床特点分析

目的 分析和总结强直性肌营养不良1型(myotonic dystrophy type 1,DM1)患者的临床特点,以提高对该病复杂临床表现的认识水平.方法 选取2009-2012年在作者医院收治并经分子诊断确诊为DM1的患者45例,回顾性分析其临床资料.结果 45例中27例有阳性家族史.首发症状以握拳后放松困难最常见(24/45).肌强直、肌无力、肌萎缩的发生率分别为95.56％、93.33％、75.56％,主要以头面诸肌、颈肌、肢体远端受累明显.除骨骼肌外,DM1还可累及眼睛(晶状体)、心脏(主要为传导系统)、中枢神经系统、颅骨、内分泌、呼吸系统等,临床表现多样.结论 典型的DM1为青中年隐袭起病,阳性家族史有助于诊断.肌强直以舌肌和大鱼际最敏感,叩击这两个部位有助于不典型肌强直症状的检出.骨骼肌以外,白内障发生率最高,对本病有一定的提示作用.男性早秃和斧头脸为本病突出的面部特征.对于怀疑DM1的患者,应及早开展遗传咨询.对于诊断DM1的患者,应全面评估并尽早处理多系统损害(尤其对于心脏和呼吸系统),同时进行定期随访复查.     

Laboratory abnormalities in ambulatory patients with myotonic dystrophy type 1

BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most prevalent form of adult muscular dystrophy worldwide. Although well known for the classic manifestations of myotonia, weakness, and early cataracts, it has broad effects on multiple organ systems. OBJECTIVE: To analyze and compile the laboratory abnormalities of 126 adult patients with DM1. DESIGN: Laboratory data obtained before treatment were compiled and include values for 45 different laboratory tests and 2860 total studies. SETTING: University hospital. PATIENTS: One hundred twenty-six medically healthy, mild to moderately affected, ambulatory patients with DM1 and good venous access enrolled in one of 12 major DM1 clinical trials at a university hospital from 1975 to 2005. RESULTS: Of the 2860 laboratory studies, results for 470 (16.4%) were outside their reference ranges. Of the 45 types of laboratory tests studied, 41 demonstrated abnormal findings. The relative frequency of an abnormally elevated laboratory value was greater than 50% in several tests, including levels of hemoglobin A(1c), follicle-stimulating hormone, luteinizing hormone in men, and gamma-glutamyltransferase and creatine kinase in women. In addition, levels of lactate dehydrogenase in men and hemoglobin in women were abnormally high or low in more than 50% of the test results evaluated. CONCLUSION: There is a high frequency of abnormal laboratory values in DM1 that may form a basis for early screening and monitoring and provide insight into the spectrum of tissues involved in this disease.     

Characterizing cognitive-motor impairments in patients with myotonic dystrophy type 1

Myotonic Dystrophy Type 1 (DM1) is the most frequent hereditary, adult-onset muscular dystrophy. Nevertheless, DM1-associated cognitive-motor impairments have not been fully characterized so far. This study aimed at profiling cognitive and locomotor dysfunctions in these patients. In addition, cognitive-motor interactions were assessed using a dual-task paradigm. Comprehensive cognitive-motor impairment profiles were generated for 19 patients with DM1 and 19 healthy subjects by thorough clinical, biomechanical and neuropsychological examinations. Detailed gait analysis was performed using a 3D motion capture system, whereas cognitive function was assessed using a standardized neuropsychological test battery. Patients with DM1 showed impaired functional mobility, gait velocity and endurance. DM1-related gait pathology was mainly characterized by enhanced dynamic instability, gait variability, and restricted ankle dorsiflexion. Patients’ cognitive impairments particularly concerned attentional functions. Dual-task conditions induced gait deviations that slightly differed between patients and controls. DM1-associated cognitive impairments correlated with reduced functional mobility and impaired ankle dorsiflexion. Patients with DM1 revealed significant impairments of walking function, balance and cognitive performance. Differential cognitive-motor interference and significant interactions between cognitive and motor dysfunctions point towards a prominent role of cognition in gait performance of patients with DM1.     

Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1

Rakocevic Stojanovic V, Peric S, Lavrnic D, Popovic S, Ille T, Stevic Z, Basta I, Apostolski S. Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1.
Acta Neurol Scand: 2010: 121: 94–98.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non‐diabetic patients with myotonic dystrophy type 1 (DM1). Materials and methods – This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI). Results – DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 ± 6.6 ng/ml vs 3.6 ± 2.9 ng/ml in men, and 13.9 ± 10.0 ng/ml vs 10.9 ± 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01). Conclusions – The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.     

Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1

Cardiac tachyarrhythmias have rarely been studied in young patients with myotonic dystrophy type 1 (DM1). The authors observed major cardiac rhythm disturbances in 11 patients aged 10 to 18 years. Tachyarrhythmic events were more frequent than impulse conduction disorders. Wide variations in CTG expansion were observed among the population. Since physical exercise was a prominent arrhythmogenic factor, systematic exercise tests with EKG monitoring may be indicated in young patients with DM1.