Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease.

BACKGROUND: Tay-Sachs disease (TSD) is an inherited neurodegenerative disorder caused by a lysosomal ß-hexosaminidase A deficiency due to mutations in the HEXA gene. The late-onset form of disease (LOTS) is considered rare, and only a limited number of cases have been reported. The clinical course of LOTS differs substantially from classic infantile TSD. METHODS: Comprehensive data from 14 Czech patients with LOTS were collated, including results of enzyme assays and genetic analyses. RESULTS: 14 patients (9 females, 5 males) with LOTS were diagnosed between 2002 and 2018 in the Czech Republic (a calculated birth prevalence of 1 per 325,175 live births). The median age of first symptoms was 21 years (range 10-33 years), and the median diagnostic delay was 10.5 years (range 0-29 years). The main clinical symptoms at the time of manifestation were stammering or slurred speech, proximal weakness of the lower extremities due to anterior horn cell neuronopathy, signs of neo- and paleocerebellar dysfunction and/or psychiatric disorders. Cerebellar atrophy detected through brain MRI was a common finding. Residual enzyme activity was 1.8-4.1% of controls. All patients carried the typical LOTS-associated c.805G>A (p.Gly269Ser) mutation on at least one allele, while a novel point mutation, c.754C>T (p.Arg252Cys) was found in two siblings. CONCLUSION: LOTS seems to be an underdiagnosed cause of progressive distal motor neuron disease, with variably expressed cerebellar impairment and psychiatric symptomatology in our group of adolescent and adult patients. The enzyme assay of ß-hexosaminidase A in serum/plasma is a rapid and reliable tool to verify clinical suspicions.

Fear-avoidance beliefs are associated with a high fat content in the erector spinae: a 1.5 tesla magnetic resonance imaging study.

Background: Intramuscular adipose tissue (IMAT) is a feature of degenerative muscle composition and is a common feature in populations with chronic low back pain (CLBP). Avoidance behavior is a possible cause of morphological muscle composition due to disuse of the paraspinal muscles. Therefore it is of clinical interest to determine the association between fear-avoidance beliefs and IMAT of the paraspinal muscles in populations with CLBP. Methods: In this cross-sectional study, we examined twenty-four adults, featuring a mean age of 48.63 years (SD ± 14.73), with CLBP. Axial T2-weighted Magnetic Resonance Imaging (MRI) images were selected on the same level as the intervertebral disc of segments L4-L5 and L5-S1. After determine the region of interest, the amount of IMAT was measured by an automatic-threshold method to distinguish fat from muscle tissue. Fear-avoidance beliefs were measured with the Fear-Avoidance Beliefs Questionnaire, with regard to Physical Activity (FABQ-PA). Bivariate correlation and multiple regression analysis were used to determine the association between IMAT of the paraspinal muscles and fear-avoidance beliefs. Results: There is a significant bivariate association between the FABQ-PA and ES IMAT (r = 0.484, P = 0.017), but not for LMM (r = 0.228, P = 0.284). The association between the FABQ-PA and ES IMAT remained moderate after adjusting for covariates (ß = 0.381, P = 0.028). Conclusion: Fear-avoidance beliefs are moderately associated with ES IMAT and poorly associated with LMM IMAT in a population with CLBP. Results should be interpreted with caution due to a small and selected study population.

Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study.

BACKGROUND: There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. METHODS: Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial-ankle pulse wave velocity was measured as an index of arterial stiffness. RESULTS: Both sarcopenic indices were modestly but significantly associated with brachial-ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. CONCLUSIONS: Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.

Psychomotor retardation caused by a defective thyroid hormone transporter: report of two families with different MCT8 mutations.

BACKGROUND/AIMS: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. CASE REPORT AND RESULTS: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. CONCLUSION: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.

Low body mass index is associated with impaired quality of life in patients with rheumatoid arthritis.

AIM: To investigate the relationship between quality of life (QOL) and rheumatoid chachesia, malnutrition in patients with rheumatoid arthritis (RA). METHODS: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) and Japanese Health Assessment Questionnaire (JHAQ) scores, body mass index (BMI), arm muscle area (AMA) and clinical indicators were measured in 385 RA patients. One-way analysis of variance for obtained data was conducted among three groups: 131 with low BMI (< 20), 163 with moderate (20-25) and 91 with high BMI (≥25). Then multiple regression analyses for JHAQ and EQ5D scores with nutritional and clinical indicators as independent variables were performed. RESULTS: EQ5D and JHAQ scores were significantly lower and higher, respectively, in the low BMI group than those in the moderate BMI group. Clinical indicators including doses of corticosteroid were similar among the three groups except for disease duration. Disease activity score (DAS) 28, disease duration, C-reactive protein and AMA were significant variables in the regression model for EQ5D. CONCLUSION: Low BMI deteriorates the QOL of RA patients. Muscle protein loss apparently leads to a reduction in BMI and QOL.

Association between muscle mass and disability in performing instrumental activities of daily living (IADL) in community-dwelling elderly in Japan.

This study describes the association between low muscle mass and disability in performing IADL in elderly, community-dwelling Japanese subjects. Subjects were 1268 elderly, community-dwelling Japanese aged 65 years or older. Low muscle mass was defined by appendicular muscle mass index (AMI, weight [kg]/height [m(2)]), measured by bioelectrical impedance analysis (BIA). We classified "middle" AMI as a value 1-2 standard deviation (SD) below the young normal mean of AMI and "low" as more than 2 SD below the young normal mean. Examination of IADL was performed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) questionnaire. In this study, 17.2% and 26.2% of elderly men and women, respectively, were classified as having low muscle mass. There was a significant association with age and the change from normal to middle to low muscle mass in both men and women. The prevalence of IADL disability also increased significantly as muscle mass decreased. After adjustment for age and BMI, low muscle mass was significantly associated with IADL disability in men and women. Furthermore, middle muscle mass was significantly associated with IADL disability in women. This study revealed that low muscle mass, defined as a value 2 SD below the mean of young adults, had a significant association with IADL disability in elderly Japanese. Interventions to prevent age-related losses in muscle mass may be an effective strategy to prevent IADL disability among the elderly.

A Kinect-based system for physical rehabilitation: a pilot study for young adults with motor disabilities.

This study assessed the possibility of rehabilitating two young adults with motor impairments using a Kinect-based system in a public school setting. This study was carried out according to an ABAB sequence in which A represented the baseline and B represented intervention phases. Data showed that the two participants significantly increased their motivation for physical rehabilitation, thus improving exercise performance during the intervention phases. Practical and developmental implications of the findings are discussed.

Metabolic profile and quality of life in class I sarcopenic overweight and obese postmenopausal women: a MONET study.

Sarcopenia is believed to be associated with disability and metabolic complications. The objective of this study was to examine the metabolic and quality-of-life profile of sarcopenic overweight and obese postmenopausal women. In this cross-sectional study of 136 healthy overweight and obese postmenopausal women, 9 class I sarcopenic women were identified. Class I sarcopenia was defined as an appendicular lean body mass index (ALBMI)

Diabetes, sarcopenia, and frailty.

Frailty is a pre-disability condition. It now can be defined clinically. The major factors leading to frailty are sarcopenia and a decline in executive function. Stressors precipitate frail individuals into a state of disability. Diabetics develop the conditions necessary for frailty earlier than other aging individuals. Appropriate treatment of diabetes mellitus and frailty precursors can result in a slowing of the aging process.

Sarcopenia and frailty in geriatric patients: implications for training and prevention.

Sarcopenia, the loss of muscle mass and strength, is a constant phenomenon in aging. Physiologic age-dependent changes (drop in growth hormone (GH), IGF-1, menopause/andropause) explain the impaired protein synthesis, the decline of muscle mass, strength, and bone density. Harmful consequences of sarcopenia in old age are loss of muscle strength, inducing itself loss of mobility, neuromuscular impairment, and homeostatic balance failure syndrome with gait and balance disorders. All these sarcopenia-induced disabilities are important factors for an increased rate of falls and fractures in old age. Both falls and fractures cause hospitalisation and immobilisation which again induces sarcopenia. Once the physiological age-dependent decline of protein synthesis has started, some connected "vicious loops" occur in frail elderly patients, forming a typical pattern in geriatric medicine. There is a vicious loop between sarcopenia and immobilisation: sarcopenia --> neuromuscular impairment --> falls and fractures --> immobilisation --> sarcopenia. Another loop is the "nutritional" vicious loop between sarcopenia and malnutrition: sarcopenia --> immobilisation --> decline of nutrition skills ("empty refrigerator") --> malnutrition --> impaired protein synthesis --> sarcopenia. There is also a third "metabolic" vicious loop between sarcopenia and the decline of the protein reserve of the body: sarcopenia --> decline of the protein reserve of the body --> diminished capacity to meet the extra demand of protein synthesis associated with disease and injury --> sarcopenia. Frailty, a term not precisely defined, results from these different "vicious loops" including sarcopenia, neuromuscular impairment, falls and fractures, immobilisation, malnutrition, impaired protein synthesis, and decreased protein reserve of the body. Implications for training: main possibilities for training and prevention (of sarcopenia and frailty) are: a) continuous neuromuscular training (including training of balance) b) mobilisation c) prevention of falls d) training of nutrition skills and improvement of nutrition e) improvement of the impaired protein synthesis (with hormones etc.), and f) avoidance of dangerous drugs (drugs which cause neuromuscular impairment).

[Peripheral muscle dysfunction in chronic obstructive pulmonary disease]. / Dysfonction musculaire périphérique dans la bronchopneumopathie chronique obstructive.

Patients with chronic obstructive pulmonary disease (COPD) often develop systemic complications of their disease. Peripheral muscle dysfunction is one such complication and is characterised by atrophy, weakness, and low oxidative capacity. These muscle changes influence exercise tolerance and quality of life independent of the impairment in lung function. In the following article, the evidence for peripheral muscle dysfunction in patients with COPD and the possible clinical implications of this problem will be discussed. Lastly, the available therapeutic options to improve peripheral muscle function in COPD will be reviewed.

Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial.

OBJECTIVE: To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation. DESIGN: Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec. RESULTS: Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7. CONCLUSIONS: Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living.

Sarcopenia and decreased muscle strength in the elderly woman: resistance training as a safe and effective intervention.

A principle component of age-related weakness and frailty in women is sarcopenia. This decrease in skeletal muscle mass is a progressive syndrome that will affect the quality of life for elderly women by decreasing the ability to perform many activities of daily living. Strength training is known to be an effective means of increasing muscular strength and size in many populations, and can be utilized successfully to significantly improve muscle strength, muscle mass and functional mobility in elderly women up to the age of 96 years. Such exercise can minimize the syndrome of physical frailty due to decreased muscle mass and strength. Any rehabilitation or exercise program for the elderly woman would benefit from the inclusion of such a training regime.

An integrated medical and psychiatric approach to conversion symptoms in a four-year-old.

Conversion disorder is a challenging diagnosis in children and adolescents. Medical and psychiatric diagnoses need to be evaluated both separately and in relation to each other. This case highlights both the diagnostic criteria for a conversion disorder in a young child and the need for an integrated medical and psychiatric approach by physicians.

Neuropsychological performance of children with Duchenne muscular dystrophy and spinal muscle atrophy.

Neuropsychological examinations were conducted on 39 boys with Duchenne muscular dystrophy (DMD) and 12 children with spinal muscular atrophy (SMA). There were no significant group differences in the pattern or level of test-score profiles, indicating that the performances of the two patient groups were very similar. However, pattern analysis indicated that while scores on verbal and non-verbal intelligence tests were within the average range for the children with DMD, there were deficits on tests of immediate memory.

[Progressive motor disability in spinal muscular atrophy. Psychosocial aspects and rehabilitation in adolescents and adults]. / La disabilità motoria progressiva nelle atrofie muscolari spinali. Aspetti psicosociali e riabilitazione negli adolescenti e negli adulti.

After a description of the principal clinical patterns of spinal muscular atrophies, the Authors discuss the aetiopathogenesis, diagnosis, articular, muscular, respiratory, whole functional and psychological evaluation, premises and aims of rehabilitation of patients with progressive motor disability. Rehabilitation techniques (postural education, prescription of braces, passive and active movements, respiratory physiotherapy) are described. The Authors assume that the role and effects of treatment vary a great deal, depending on the individual case and the moments of psychological crises. Rehabilitation may delay deterioration and achieve the prevention of evolutional complications: successful results are obtained if the patients and family are given detailed instructions for treatment at home and if a relationship and a close cooperation between the patient and the physiotherapist are established. Specific information and psychological support should be provided, which will cover not only the technical aspects of rehabilitation, but also the concrete problems of daily life and of adjustment in family and society.